367 results on '"Masanori Asakura"'
Search Results
102. Use of serum fibroblast growth factor 23 vs. plasma B-type natriuretic peptide levels in assessing the pathophysiology of patients with heart failure
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Toshihisa Anzai, Yasuo Sugano, Takahiro Ohara, Makoto Amaki, Naoki Mochizuki, Miki Imazu, Hiroshi Asanuma, Masafumi Kitakaze, Hideaki Kanzaki, Hiroyuki Takahama, Masanori Asakura, and Takuya Hasegawa
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Male ,medicine.medical_specialty ,Physiology ,medicine.drug_class ,Hemodynamics ,Renal function ,Blood Pressure ,Vena Cava, Inferior ,030204 cardiovascular system & hematology ,Inferior vena cava ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine.artery ,Natriuretic Peptide, Brain ,Internal Medicine ,medicine ,Natriuretic peptide ,Humans ,Pulmonary Wedge Pressure ,cardiovascular diseases ,030212 general & internal medicine ,Pulmonary wedge pressure ,Aged ,Heart Failure ,business.industry ,Middle Aged ,medicine.disease ,Fibroblast Growth Factors ,Fibroblast Growth Factor-23 ,stomatognathic diseases ,Endocrinology ,medicine.vein ,Echocardiography ,Heart failure ,Heart catheterization ,Pulmonary artery ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Recently, fibroblast growth factor 23 (FGF23), a phosphate-regulating hormone, has been linked to the pathophysiology of heart failure (HF), thus encouraging us to examine which hemodynamic abnormalities of HF are linked to either serum FGF23 or plasma B-type natriuretic peptide (BNP) levels. We measured both the serum FGF23 and plasma BNP levels in 154 consecutive prospectively enrolled hospitalized HF patients, with an estimated glomerular filtration rate >40 ml min−1 1.73 m−2, who underwent heart catheterizations and an echocardiogram. The serum FGF23 levels correlated with the diameter of the inferior vena cava and its respiratory changes, whereas the plasma BNP levels did not. Both the plasma BNP and serum FGF23 levels were moderately correlated with the mean pulmonary artery (PA) pressure and pulmonary capillary wedge (PCW) pressure. Interestingly, in patients with an above-median right-atrial (RA) pressure (4 mm Hg), FGF23 levels were correlated with both PA and PCW pressures, but the levels were not correlated in patients with a below-median RA pressure. In contrast, the plasma BNP levels were correlated with both PA and PCW pressures. Finally, serum FGF23 levels, compared with the plasma BNP levels, were more strongly associated with the clinical outcomes in patients with above-median RA pressure. These findings suggested that serum FGF23 levels are predominantly correlated with clinical outcomes, may serve as a biomarker for HF in patients with higher RA pressure, may provide beneficial information for patients with right-sided HF and may represent different clinical information than that provided only by plasma BNP levels.
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- 2016
103. Chemical Endoplasmic Reticulum Chaperone Alleviates Doxorubicin-Induced Cardiac Dysfunction
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Masaki Yamato, Masafumi Kitakaze, Yoshihiro Asano, Takashi Matsuzaki, Keiji Okuda, Yulin Liao, Brent A. French, Tetsuo Minamino, Ryo Araki, Hiroshi Asanuma, Hai Ying Fu, Shota Tsuchida, Shoji Sanada, Masanori Asakura, and Yasushi Sakata
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Male ,0301 basic medicine ,medicine.medical_specialty ,Physiology ,Antineoplastic Agents ,Endoplasmic Reticulum ,Phenylbutyrate ,Cardiac dysfunction ,Mice ,03 medical and health sciences ,Internal medicine ,medicine ,Animals ,Myocytes, Cardiac ,Doxorubicin ,Cells, Cultured ,Heart Failure ,Mice, Inbred ICR ,Cardiotoxicity ,biology ,Endoplasmic reticulum ,Endoplasmic Reticulum Stress ,medicine.disease ,Phenylbutyrates ,Rats ,030104 developmental biology ,Endocrinology ,Apoptosis ,Chaperone (protein) ,Heart failure ,biology.protein ,Cancer research ,Cardiology and Cardiovascular Medicine ,medicine.drug - Abstract
Rationale: Doxorubicin is an effective chemotherapeutic agent for cancer, but its use is often limited by cardiotoxicity. Doxorubicin causes endoplasmic reticulum (ER) dilation in cardiomyocytes, and we have demonstrated that ER stress plays important roles in the pathophysiology of heart failure. Objective: We evaluated the role of ER stress in doxorubicin-induced cardiotoxicity and examined whether the chemical ER chaperone could prevent doxorubicin-induced cardiac dysfunction. Methods and Results: We confirmed that doxorubicin caused ER dilation in mouse hearts, indicating that doxorubicin may affect ER function. Doxorubicin activated an ER transmembrane stress sensor, activating transcription factor 6, in cultured cardiomyocytes and mouse hearts. However, doxorubicin suppressed the expression of genes downstream of activating transcription factor 6, including X-box binding protein 1. The decreased levels of X-box binding protein 1 resulted in a failure to induce the expression of the ER chaperone glucose-regulated protein 78 which plays a major role in adaptive responses to ER stress. In addition, doxorubicin activated caspase-12, an ER membrane–resident apoptotic molecule, which can lead to cardiomyocyte apoptosis and cardiac dysfunction. Cardiac-specific overexpression of glucose-regulated protein 78 by adeno-associated virus 9 or the administration of the chemical ER chaperone 4-phenylbutyrate attenuated caspase-12 cleavage, and alleviated cardiac apoptosis and dysfunction induced by doxorubicin. Conclusions: Doxorubicin activated the ER stress–initiated apoptotic response without inducing the ER chaperone glucose-regulated protein 78, further augmenting ER stress in mouse hearts. Cardiac-specific overexpression of glucose-regulated protein 78 or the administration of the chemical ER chaperone alleviated the cardiac dysfunction induced by doxorubicin and may facilitate the safe use of doxorubicin for cancer treatment.
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- 2016
104. Evaluation of the safety and efficacy of TY-51924 in patients with ST elevated acute myocardial infarction – Early phase II first in patient pilot study
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Akira Kaneko, Takafumi Hiro, Toshiaki Yokoi, Shigeru Fukuzawa, Masaaki Uematsu, Yasunori Ueda, Koichi Nakao, Haruo Hirayama, Masanori Asakura, Takahito Sone, Kazuo Kimura, Atsushi Hirayama, Masami Kosuge, Naoya Matsumoto, Tadateru Takayama, and Masaharu Ishihara
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Adult ,Male ,medicine.medical_specialty ,Sodium-Hydrogen Exchangers ,medicine.medical_treatment ,Myocardial Infarction ,Myocardial Reperfusion Injury ,Pilot Projects ,Acute myocardial infarction ,Cardioprotection ,Sulfuric Acid Esters ,030204 cardiovascular system & hematology ,Single-photon emission computed tomography ,Lower risk ,Guanidines ,Percutaneous coronary intervention ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Myocardial infarction ,NHE inhibitor ,Aged ,Tomography, Emission-Computed, Single-Photon ,Dose-Response Relationship, Drug ,medicine.diagnostic_test ,business.industry ,Myocardium ,Neurotoxicity ,Middle Aged ,medicine.disease ,Reperfusion injury ,Acute Disease ,Cardiology ,Female ,business ,Cardiology and Cardiovascular Medicine - Abstract
Background In myocardial ischemia–reperfusion injuries, the involvement of the Na + /H + exchanger (NHE) is considered to be one of the pathogenic mechanisms following reperfusion. TY-51924 is a novel hydrophilic NHE inhibitor with a lower risk of central neurotoxicity than previous NHE inhibitors. This open-label, dose-escalating study was undertaken to investigate the safety, efficacy, and pharmacokinetics of TY-51924 in patients with ST-elevation myocardial infarction (STEMI). Methods Consent was obtained from a total of 30 patients with first anterior STEMI. After 12 patients were determined to be ineligible, the remaining 18 patients, each of whom was undergoing primary percutaneous coronary intervention (pPCI), received TY-51924 intravenously up to 10, 20, or 30 mg/kg as the low-, medium-, or high-dose groups, respectively ( n = 6 in each group). The primary endpoints were safety (up to 7 days) and plasma drug concentration. The myocardial salvage index (MSI) was measured by 201 Tl/ 123 I-beta-methyl- p -iodophenyl pentadecanoic acid single photon emission computed tomography (SPECT) 3–5 days after pPCI. Results No side effects were observed. Plasma drug concentrations increased dose-dependently, and were subsequently eliminated rapidly. MSIs were 0.118, 0.335, and 0.192 in the low-, medium-, and high-dose groups, respectively. In additional analysis, the combined MSIs in the medium- and high-dose groups were significantly higher than those in the low-dose group, in patients with a longer time from symptom onset to reperfusion ( p = 0.0247). Conclusions No side effects were observed even at the highest dose with this novel hydrophilic NHE inhibitor. Therefore, TY-51924 is thought to be safe in patients with STEMI, even at the highest dose. Potential cardioprotective effects of intravenous TY-51924 might be expected based on the results obtained for the MSIs using SPECT at 20–30 mg/kg. However, further large-scale, double-blind, placebo-controlled clinical studies are required to confirm the efficacy and safety implied in the current study.
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- 2016
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105. Four cases of investigational therapy with interleukin-11 against acute myocardial infarction
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Yasukatsu Izumi, Yasushi Fujio, Masashi Nakagawa, Minoru Yoshiyama, Kenichi Sugioka, Suwako Fujita, Satoshi Nishimura, Asahiro Ito, Yasuko Owada, Makiko Maeda, Yoshiki Sawa, Takashi Daimon, Shinichi Iwata, Kazuki Mizutani, Daisaku Nakatani, Shinichi Nonin, and Masanori Asakura
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Male ,0301 basic medicine ,medicine.medical_specialty ,Pathology ,Cardiotonic Agents ,medicine.medical_treatment ,030204 cardiovascular system & hematology ,Coronary Angiography ,Ventricular Function, Left ,03 medical and health sciences ,Percutaneous Coronary Intervention ,0302 clinical medicine ,Internal medicine ,Humans ,Medicine ,cardiovascular diseases ,Myocardial infarction ,Aged ,Cytokine Therapy ,business.industry ,Percutaneous coronary intervention ,Stroke Volume ,Drugs, Investigational ,Recovery of Function ,Vascular surgery ,Interleukin-11 ,medicine.disease ,Myocardial Contraction ,Recombinant Proteins ,Cardiac surgery ,Treatment Outcome ,030104 developmental biology ,Coronary occlusion ,Heart failure ,Conventional PCI ,Cardiology ,ST Elevation Myocardial Infarction ,Administration, Intravenous ,Cardiology and Cardiovascular Medicine ,business - Abstract
We describe four cases of the patients with ST-elevation myocardial infarction (STEMI) that were treated with interleukin-11 (IL-11), a cardioprotective cytokine. Recombinant human IL-11 (rhIL-11), was intravenously administered to two cases at low dose (6 µg/kg) and to two at high dose (25 µg/kg). The cytokine administration started just after the coronary occlusion was confirmed by coronary angiography (CAG), taking 3 h. Following CAG, percutaneous coronary intervention (PCI) was performed as a standard therapy. No serious adverse drug reactions were observed. All the cases left the hospital without the symptom of heart failure. We discuss the possibility of the clinical use of rhIL-11 as an adjunct therapy to PCI for the STEMI patients.
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- 2016
106. Azilsartan, but not Candesartan Improves Left Ventricular Diastolic Function in Patients with Hypertension and Heart Failure
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Takuya Hasegawa, Hideaki Kanzaki, Yasuo Sugano, Toshihisa Anzai, Takahiro Ohara, Makoto Amaki, Masafumi Kitakaze, Atsushi Nakano, Mari Sakamoto, and Masanori Asakura
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medicine.medical_specialty ,Ejection fraction ,business.industry ,Diastole ,heart failure ,lcsh:Geriatrics ,brain natriuretic peptide ,medicine.disease ,Brain natriuretic peptide ,lcsh:RC952-954.6 ,Candesartan ,Blood pressure ,Heart failure ,Internal medicine ,Azilsartan ,medicine ,Cardiology ,echocardiography ,diastolic dysfunction ,In patient ,angiotensin receptor blocker ,Geriatrics and Gerontology ,business ,medicine.drug - Abstract
Summary Background Diastolic dysfunction is a major cause of heart failure (HF) with a preserved ejection fraction (HFpEF); however, there is no clear strategy for treating diastolic dysfunction. Myocardial and vascular abnormalities may cause HFpEF, which indicates that correcting both abnormalities may specifically improve the severity of diastolic dysfunction. Candesartan primarily affects the myocardium, but azilsartan affects the myocardium and the aortic vasculature. This study was undertaken to test the hypothesis that azilsartan, but not candesartan, improves left ventricular (LV) diastolic dysfunction in patients with hypertension and HFpEF. Methods Among patients with HF in our database, the patients who received azilsartan or candesartan were retrospectively screened. Fifteen patients treated with azilsartan were identified, and sex-matched patients who received candesartan were blindly selected. Results At baseline, there were no significant differences between the two groups in clinical findings, echocardiographic parameters, and plasma brain natriuretic peptide levels. At 3–6 months, blood pressure decreased to similar levels in both groups. However, the early LV filling velocity/early diastolic velocity (E/e′) ratio decreased in the azilsartan group (13.0 ± 4.2 vs. 10.9 ± 3.2, p = 0.03), but remained unchanged in the candesartan group (12.0 ± 3.6 vs. 12.5 ± 5.0, p = 0.58; for interaction, p = 0.04). Other echocardiographic parameters were unaltered by azilsartan or candesartan. Conclusion Azilsartan improves diastolic function in HF patients with hypertension, and it may be the preferred option over other angiotensin II receptor blockers in patients with HFpEF.
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- 2015
107. COMPARISON OF SEVERITY IN NON-CULPRIT LESION BETWEEN STEMI AND NSTEMI
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Toshio Kimura, Masanori Asakura, Kojiro Miki, Nagataka Yoshihara, Koji Yanaka, Hirokuni Akahori, Takamasa Tanaka, Takahiro Imanaka, and Masaharu Ishihara
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medicine.medical_specialty ,business.industry ,medicine.disease ,Coronary artery disease ,Lesion ,Culprit lesion ,Internal medicine ,medicine ,Cardiology ,cardiovascular diseases ,Myocardial infarction ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Abstract
Previous studies have reported that long-term prognosis of non-ST-elevation myocardial infarction (NSTEMI) was worse than that of ST-elevation myocardial infarction (STEMI). We hypothesized that coronary artery disease (CAD) in non-culprit lesion is more severe in NSTEMI. We compared with the
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- 2020
108. Overexpression of Na+-HCO3– cotransporter contributes to the exacerbation of cardiac remodeling in mice with myocardial infarction by increasing intracellular calcium overload
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Yulin Liao, Lu Chen, Fang Xi, Masafumi Kitakaze, Wangjun Liao, Hailin Zhu, Lin Chen, Mengjia Shen, Kaitong Chen, Jianping Bin, Jie Liu, Zhenhuan Chen, Masanori Asakura, Yingqi Zhu, Xiaobo Huang, Qiancheng Wang, Yuegang Wang, and Hairuo Lin
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0301 basic medicine ,medicine.medical_specialty ,Chemistry ,chemistry.chemical_element ,030204 cardiovascular system & hematology ,Hypoxia (medical) ,Calcium ,medicine.disease ,Calcium in biology ,Contractility ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Endocrinology ,Apoptosis ,Internal medicine ,medicine ,Ventricular pressure ,Molecular Medicine ,Myocardial infarction ,medicine.symptom ,Molecular Biology ,Intracellular - Abstract
The role of the cardiac isoform of the electrogenic sodium-bicarbonate ion cotransporter (NBCe1) in cardiac remodeling is not fully understood. The aim of this study was to assess the effects of NBCe1 overexpression on cardiac remodeling induced by myocardial infarction (MI) in mice. We generated NBCe1 transgenic (Tg) mice and NBCe1 overexpressing adult mouse ventricular myocytes (AMVMs) to investigate the role of NBCe1 on post-MI remodeling and calcium kinetics. Tg mice showed a markedly higher mortality rate and larger infarct size after MI. At 6 weeks after MI, the maximum rising rates of left ventricular pressure (dp/dt), contractility index, and the exponential time constant of relaxation (τ) were markedly lower, and there was higher cardiomyocyte apoptosis, in Tg mice compared with WT mice. In cultured AMVMs, overexpression of NBCe1 decreased sarcomere shortening and calcium amplitude. In WT AMVMs, the rates of the rise and decay phase of calcium transients, indicated by the rising time (Tpeak, time to peak) and decay time constant (τd), and the number of apoptotic cells, were increased following hypoxia, while overexpression of NBCe1 further increased Tpeak and cellular apoptosis, but not τd. Intracellular resting calcium and sodium concentrations were significantly increased following both hypoxia and NBCe1 overexpression. Co-treatment with S0859, an NBCe1 antagonist, blocked the hypoxia-induced increase in Tpeak, τd, intracellular resting calcium and sodium concentrations, and apoptosis in cardiomyocytes. These findings indicate that NBCe1 overexpression promotes cardiac remodeling by increasing intracellular calcium overload. Therefore, NBCe1 should be a potential target for treatment of cardiac remodeling.
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- 2020
109. SIGNIFICANCE OF NEW SIMPLE ECHOCARDIOGRAPHIC PARAMETER FOR MITRAL REGURGITATION SEVERITY IN ATRIAL FIBRILLATION
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Akiko Goda, Masaharu Ishihara, Kumiko Masai, Masanori Asakura, Yoshiro Naito, and Aika Daimon
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medicine.medical_specialty ,Mitral regurgitation ,business.industry ,Atrial fibrillation ,medicine.disease ,Simple (abstract algebra) ,Internal medicine ,LV outflow ,cardiovascular system ,medicine ,Cardiology ,Velocity time integral ,cardiovascular diseases ,Cardiology and Cardiovascular Medicine ,business - Abstract
Left ventricular early inflow-outflow index (LVEIO), which is calculated by dividing the mitral E-wave velocity by the LV outflow velocity time integral has been proposed as a parameter for severity of mitral regurgitation (MR). We have reported that LVEIO is a useful and simple method to diagnose
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- 2020
110. IMPACT OF POLYVASCULAR DISEASE ON SEVERITY OF CORONARY ARTERY DISEASE AND CLINICAL OUTCOME IN PATIENTS WITH STABLE ANGINA
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Koji Yanaka, Takamasa Tanaka, Nagataka Yoshihara, Hirokuni Akahori, Toshio Kimura, Masanori Asakura, Kojiro Miki, Takahiro Imanaka, and Masaharu Ishihara
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Polyvascular disease ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Percutaneous coronary intervention ,medicine.disease ,Stable angina ,Coronary artery disease ,Internal medicine ,Conventional PCI ,medicine ,Cardiology ,In patient ,cardiovascular diseases ,Cardiology and Cardiovascular Medicine ,business - Abstract
This study sought to assess the impact of polyvascular disease on severity of coronary artery disease (CAD) and clinical outcome in patients undergoing percutaneous coronary intervention (PCI) for stable angina. We retrospectively analyzed a single-center database of 283 patients (male 75 %, mean
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- 2020
111. The impact of peripheral artery disease on left ventricular diastolic function
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Koji Yanaka, Takahiro Imanaka, Nagataka Yoshihara, Kojiro Miki, Tohru Masuyama, Takamasa Tanaka, Masaharu Ishihara, Masanori Asakura, and Hirokuni Akahori
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Male ,medicine.medical_specialty ,Arterial disease ,Systole ,Diastole ,Disease ,030204 cardiovascular system & hematology ,Logistic regression ,Ventricular Function, Left ,03 medical and health sciences ,Peripheral Arterial Disease ,Ventricular Dysfunction, Left ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Diastolic function ,030212 general & internal medicine ,Aged ,Aged, 80 and over ,Heart Failure ,Ejection fraction ,business.industry ,Stroke Volume ,Middle Aged ,medicine.anatomical_structure ,Echocardiography ,Case-Control Studies ,Cardiology ,Female ,Ankle ,Cardiology and Cardiovascular Medicine ,Heart failure with preserved ejection fraction ,business - Abstract
Peripheral artery disease (PAD) is often accompanied by heart failure with preserved ejection fraction (HFpEF). Left ventricular (LV) diastolic dysfunction is related to HFpEF. The aim of this study was to compare LV diastolic function between patients with or without PAD.One thousand one hundred twenty-one patients (male 56%, mean age 68±13 years) with available preserved LV systolic function assessed by echocardiography (ejection fraction ≥50%) were enrolled from a single-center database between January 2013 and May 2015. PAD was defined as ankle brachial index0.9 or previous history of lower extremity bypass and/or endovascular therapy. Diagnosis of LV diastolic dysfunction was based on the American Society of Echocardiography and European Association of Cardiovascular Imaging guidelines. The prevalence of LV diastolic dysfunction was compared between patients with PAD and those without PAD. Multivariate analysis was performed by logistic regression analyses to assess predictors of LV diastolic dysfunction.Two hundred patients (18%) had PAD. Patients with PAD had higher E/e' (15.3±7.4 vs 11.8±5.5, p0.01), tricuspid regurgitation velocity (2.37±0.33 vs 2.19±0.28m/s, p0.01), left atrial volume index (40.6±20.2 vs 32.1±13.6mL/mThe prevalence of LV diastolic dysfunction was higher in patients with PAD than patients without PAD.
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- 2018
112. Effective blood hemoglobin level to predict prognosis in heart failure with preserved left ventricular ejection fraction: results of the Japanese heart failure syndrome with preserved ejection fraction registry
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Toshiyuki Nagai, Tohru Masuyama, Masataka Sugahara, Keisuke Okuno, Tomotaka Ando, Seiki Yasumura, Toshihisa Anzai, Masanori Asakura, Yoshihiko Saito, Tsutomu Yoshikawa, and Yoshiro Naito
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Male ,medicine.medical_specialty ,Multivariate analysis ,Anemia ,Prevalence ,030204 cardiovascular system & hematology ,Patient Readmission ,Ventricular Function, Left ,03 medical and health sciences ,Hemoglobins ,0302 clinical medicine ,Sex Factors ,Japan ,Risk Factors ,Internal medicine ,Cause of Death ,medicine ,Humans ,030212 general & internal medicine ,Prospective Studies ,Registries ,Aged ,Aged, 80 and over ,Heart Failure ,Ejection fraction ,business.industry ,Stroke Volume ,Vascular surgery ,Middle Aged ,medicine.disease ,Prognosis ,Survival Analysis ,Cardiac surgery ,Heart failure ,Multivariate Analysis ,Cardiology ,Female ,Hemoglobin ,Cardiology and Cardiovascular Medicine ,business - Abstract
High prevalence of anemia in heart failure with preserved left ventricular ejection fraction (HFpEF) has been reported. However, little is known about the association of anemia and gender with prognosis in HFpEF patients. In addition, effective blood hemoglobin (Hb) level for prognosis in HFpEF patients remains largely unknown. In this study, we investigated the association between anemia, gender, and prognosis in 535 HFpEF patients enrolled in Japanese heart failure syndrome with preserved ejection fraction registry. Furthermore, we assessed effective blood Hb level to predict prognosis in HFpEF patients. According to the World Health Organization criteria, the prevalence rate of anemia on admission was about 70% in both male and female HFpEF patients. Kaplan–Meier analysis for all-cause mortality demonstrated that anemic patients had poor prognosis compared with non-anemic patients in both male and female HFpEF patients. Interestingly, multivariate analysis revealed that blood Hb level at discharge was an independent predictor of all-cause mortality in both male and female HFpEF patients. According to survival classification and regression tree analysis, blood Hb level at discharge of 9.4 g/dL for male and 12.3 g/dL for female was more accurate cutoff value to predict all-cause mortality in HFpEF patients. Anemia was implicated in poor prognosis in both male and female HFpEF patients. In particular, blood Hb level at discharge was an independent predictor of all-cause mortality in both male and female HFpEF patients. Effective cutoff value of blood Hb level at discharge to predict all-cause mortality was lower in male than in female HFpEF patients.
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- 2018
113. Abstract 542: Manipulation of Beta Adrenergic Receptor in Pressure-Overloaded Murine Hearts Mimics Adverse Cardiac Remodeling and Reverse Remodeling
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Masanori Asakura, Koichi Nishimura, Yoshitaka Okuhara, Tohru Masuyama, Shinichi Hirotani, Yoshiro Naito, and Masaharu Ishihara
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Pressure overload ,medicine.medical_specialty ,Adrenergic receptor ,Physiology ,business.industry ,Heart failure ,Internal medicine ,Cardiology ,Medicine ,Cardiology and Cardiovascular Medicine ,business ,medicine.disease ,Reverse remodeling - Abstract
Background: Adverse cardiac remodeling (ACR) during pressure overload is a major concern in development of heart failure (HF). Cardiac reverse remodeling (CRR) normally occurs following induction of beta-receptor blockade and is linked to improved prognosis of HF. However, the detailed and regulatory mechanisms of both ACR and CRR remain to be fully elucidated. To solve these issues, a novel highly reproducible model that mimics these pathophysiological conditions is needed. Methods and results: We explored suitable experimental conditions for establishing a highly reproducible model that mimics adverse cardiac remodeling. To examine suitable durations of transverse aortic constriction (TAC) before one-week infusion of ISO (3mg/kg/day), mice were distributed into three groups according to TAC durations. Proportion of adverse cardiac remodeling was 44.4% (4 of 9) in one-week, 60.0% (6 of 10) in two-week, and 91.7% (11 of 12) in three-week TAC groups. Next we examined adequate dose of ISO infusion after three weeks of TAC. Proportion of adverse cardiac remodeling was 37.5% (3 of 8) in 1mg/kg/day, 83.3% (5 of 6) in 3mg/kg/day, and 100% (8 of 8) in 10mg/kg/day group. But infusion of 10mg/kg/day ISO caused an increase in systolic BP. Thus we identified 3-week TAC and subsequent one-week ISO (3mg/kg/day) infusion as a suitable model for ACR. To identify molecular signatures of failing hearts of our ACR model, we performed RNA-Seq analyses. We found the up-regulated genes were mainly related to fibrosis including Fbn1 , C1qtnf6 and Loxl2 and the down-regulated genes associated with mitochondrial functions including, Uqcrc1 , Ndufs3 , and Idh2 . Next, we followed the changes in cardiac function after ceasing ISO to investigate CRR. Decreased LVFS gradually recovered to baseline within 7 weeks after cessation of ISO and exhibited CRR. Gene expression signature of CRR hearts was almost identical to that of TAC hearts without ISO infusion. Conclusions: Our model exhibits a transition to adverse cardiac remodeling and subsequent reverse remodeling with high reproducibility. This novel mouse model might add new insights into these cardiac remodeling.
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- 2018
114. P3756Impact of anemia in patients with HFpEF with chronic kidney disease: results of Japanese heart failure syndrome with preserved ejection fraction (JASPER) registry
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Tohru Masuyama, Toshihisa Anzai, Jasper registry, Toshiyuki Nagai, Masataka Sugahara, T Yoshikawa, Yoshihiko Saito, Masanori Asakura, Tomotaka Ando, Yoshiro Naito, and Keisuke Okuno
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medicine.medical_specialty ,Ejection fraction ,business.industry ,Anemia ,Heart failure ,Internal medicine ,Cardiology ,Medicine ,In patient ,Cardiology and Cardiovascular Medicine ,business ,medicine.disease ,Kidney disease - Published
- 2018
115. P2623Transferrin receptor 1 hetero deletion attenuates angiogenesis in mouse hind limb ischemia model
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Seiki Yasumura, Keisuke Okuno, Masaharu Ishihara, Tohru Masuyama, Koichi Nishimura, Yoshiro Naito, and Masanori Asakura
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Pathology ,medicine.medical_specialty ,business.industry ,Angiogenesis ,medicine ,Cardiology and Cardiovascular Medicine ,business ,Receptor ,Hind limb ischemia - Published
- 2018
116. P5648Appropriate hemoglobin levels in HFpEF patients: results of Japanese heart failure syndrome with preserved ejection fraction (JASPER) registry
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Yoshihiko Saito, Masanori Asakura, Tohru Masuyama, Yoshiro Naito, Toshiyuki Nagai, Toshihisa Anzai, Jasper registry, T Yoshikawa, Tomotaka Ando, Masataka Sugahara, and Keisuke Okuno
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medicine.medical_specialty ,Ejection fraction ,business.industry ,Internal medicine ,Heart failure ,medicine ,Cardiology ,Hemoglobin levels ,Cardiology and Cardiovascular Medicine ,medicine.disease ,business - Published
- 2018
117. P5628Left atrial booster dysfunction and enlargement predict left atrial thrombus in patients with sinus rhythm after cardiogenic cerebral infarction
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Tohru Masuyama, Masaharu Ishihara, Akiko Goda, Yoshihiro Ohta, Takeshi Oshita, Masataka Sugahara, Masanori Asakura, Aika Daimon, Kumiko Masai, and Takanao Mine
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medicine.medical_specialty ,business.industry ,Cerebral infarction ,Internal medicine ,Cardiology ,Medicine ,Sinus rhythm ,In patient ,Cardiology and Cardiovascular Medicine ,business ,medicine.disease ,Left atrial thrombus - Published
- 2018
118. Correlates and Prognostic Values of Appearance of L Wave in Heart Failure Patients With Preserved vs. Reduced Ejection Fraction
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Akiko Goda, Kumiko Masai, Aika Daimon, Masanori Asakura, Masataka Sugahara, Tohru Masuyama, Toshiaki Mano, and Masaharu Ishihara
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Male ,medicine.medical_specialty ,Poor prognosis ,Diastole ,030204 cardiovascular system & hematology ,03 medical and health sciences ,Ventricular Dysfunction, Left ,0302 clinical medicine ,Left atrial ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Mitral annulus ,Mitral forward flow ,Aged ,Aged, 80 and over ,Heart Failure ,Ejection fraction ,Ventricular Remodeling ,business.industry ,Stroke Volume ,General Medicine ,Middle Aged ,medicine.disease ,Prognosis ,Echocardiography, Doppler ,Heart failure ,Cardiology ,Female ,Hypertrophy, Left Ventricular ,Cardiology and Cardiovascular Medicine ,Heart failure with preserved ejection fraction ,business ,Blood Flow Velocity ,Follow-Up Studies - Abstract
Background Mid-diastolic mitral forward flow (L wave) is occasionally detected in heart failure (HF), but its correlates and prognostic value are still unknown, particularly in light of the type of HF, that is, HF with preserved or with reduced ejection fraction (HFpEF, HFrEF). Methods and Results: Of 151 patients with HF, L wave was observed in 23 of 82 HFrEF patients and in 25 of 69 HFpEF patients. Mitral early diastolic velocity (E), the ratio of E to mitral annulus velocity, and left atrial volume index were greater in the patients with L wave than in those without L wave in both subsets. Left ventricular (LV) mass index and relative wall thickness were greater in the patients with L wave than in those without L wave in the HFpEF group, but there was no difference in either parameter in the HFrEF group. Prognosis was poorer in those with L wave than in those without L wave both in the HFrEF and HFpEF groups. Conclusions Appearance of L wave is associated with the degree of LV diastolic dysfunction, but there was a difference in LV geometrical correlates of the appearance of L wave between the HFpEF and HFrEF groups. Detection of L wave is suggestive of poor prognosis independent of LVEF in HF.
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- 2018
119. Abstract 133: Heterozygous Deletion of Transferrin Receptor 1 Suppresses Angiogenesis in a Mouse Model of Hind Limb Ischemia
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Tohru Masuyama, Hisashi Sawada, Yoshiro Naito, Seiki Yasumura, Keisuke Okuno, Koichi Nishimura, Masanori Asakura, and Masaharu Ishihara
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medicine.medical_specialty ,business.industry ,Angiogenesis ,Arterial disease ,Trace mineral ,Ischemia ,Transferrin receptor ,medicine.disease ,Living body ,Endocrinology ,Internal medicine ,medicine ,Cardiology and Cardiovascular Medicine ,business ,Hind limb ischemia - Abstract
Objective: Angiogenesis can be triggered under conditions of ischemia and plays a protective role in peripheral artery disease. Iron is an essential trace mineral in the living body whose intracellular metabolism is regulated by transferrin receptor 1 (TfR1). Excess iron causes tissue damage and has been reported in patients with peripheral artery disease. Therefore, we hypothesized that TfR1 contributes to the pathophysiology of hind limb ischemia through iron overload. The aim of this study is to examine whether TfR1 deletion effects angiogenesis in hind limb ischemia. Methods and Results: Since homozygous TfR1 deletion is embryonically lethal, mice with heterozygous TfR1 deletion and their wild type littermates were used in this study. To induce hind limb ischemia, the left femoral artery in 8 - 9 week-old male mice was ligated and stripped. The non-ligated right hind limb was used as a control. Blood flow was measured by laser Doppler blood flowmetry at both a baseline of 1 hour and 28 days after the surgery. In wild type, the ratio of ischemc/non-ischemic hind limb blood flow was significantly decreased to 12% at baseline, and recovered to 62% at day 28. On the other hand, TfR1 deleted mice also showed similar reduction of blood flow at baseline, whereas blood flow recovery at day 28 was attenuated to 42%. Subsequently, both right and left adductor muscles were harvested for Western blot and immunohistochemistry. TfR1 expression in the adductor muscle was decreased in TfR1 deleted mice compared to wild type, regardless of the ligation. Ferritin, a marker for iron storage, was 10 times higher in ischemic muscles than in wild type non-ischemic muscles. In contrast, ferritin levels in TfR1 deleted mice were not altered by the surgery. Finally, immunohistochemistry for CD31 was performed to evaluate angiogenesis. The ischemic adductor muscle of TfR1 deleted mice had few CD31 positive vascular structures. Conclusions: Heterozygous deletion of TfR1 attenuated iron overload and angiogenesis in a mouse model of hind limb ischemia. TfR1 may be a novel therapeutic target for the treatment of peripheral artery disease.
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- 2018
120. The impact of creating mathematical formula to predict cardiovascular events in patients with heart failure
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Jiyoong Kim, Takashi Washio, Hiroyuki Tsutsui, Tomomi Ide, Mari Sakamoto, Masafumi Kitakaze, Shintaro Kinugawa, Shin Ito, Hiroki Fukuda, Masanori Asakura, Hiroshi Asanuma, Akira Ishii, and Arata Fukushima
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Male ,medicine.medical_specialty ,lcsh:Medicine ,Predictive capability ,Kaplan-Meier Estimate ,Mathematical formula ,030204 cardiovascular system & hematology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,In patient ,Prospective Studies ,030212 general & internal medicine ,lcsh:Science ,Prospective cohort study ,Aged ,Probability ,Retrospective Studies ,Heart Failure ,Multidisciplinary ,business.industry ,lcsh:R ,Models, Cardiovascular ,Retrospective cohort study ,Middle Aged ,Prognosis ,medicine.disease ,Heart failure ,Cardiology ,Female ,lcsh:Q ,Observational study ,business ,Algorithms - Abstract
Since our retrospective study has formed a mathematical formula, α = f(x1, …, x252), where α is the probability of cardiovascular events in patients with heart failure (HF) and x1 is each clinical parameter, we prospectively tested the predictive capability and feasibility of the mathematical formula of cardiovascular events in HF patients. First of all, to create such a mathematical formula using limited number of the parameters to predict the cardiovascular events in HF patients, we retrospectively determined f(x) that formulates the relationship between the most influential 50 clinical parameters (x) among 252 parameters using 167 patients hospitalized due to acute HF; the nonlinear optimization could provide the formula of α = f(x1, …, x50) which fitted the probability of the actual cardiovascular events per day. Secondly, we prospectively examined the predictability of f(x) in other 213 patients using 50 clinical parameters in 3 hospitals, and we found that the Kaplan–Meier curves using actual and estimated occurrence probabilities of cardiovascular events were closely correlated. We conclude that we created a mathematical formula f(x) that precisely predicted the occurrence probability of future cardiovascular outcomes of HF patients per day. Mathematical modelling may predict the occurrence probability of cardiovascular events in HF patients.
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- 2018
121. A dipeptidyl peptidase-IV inhibitor improves diastolic dysfunction in Dahl salt-sensitive rats
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Hiroshi Asanuma, Kazuhiro Shindo, Yuri Nakajima, Masanori Asakura, Miki Imazu, Satoru Yamazaki, Kyung-Duk Min, Hiroko Takahama, Shin Ito, Hiroki Fukuda, Tatsuro Hitsumoto, Masafumi Kitakaze, and Hai Ying Fu
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0301 basic medicine ,Male ,endocrine system ,medicine.medical_specialty ,animal structures ,Cardiac fibrosis ,Heart Ventricles ,Diastole ,Hemodynamics ,030204 cardiovascular system & hematology ,Kidney Function Tests ,Glucagon-Like Peptide-1 Receptor ,Renin-Angiotensin System ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Renin–angiotensin system ,medicine ,Animals ,Vildagliptin ,Molecular Biology ,Heart Failure ,Inflammation ,Dipeptidyl-Peptidase IV Inhibitors ,Rats, Inbred Dahl ,business.industry ,Myocardium ,Stroke Volume ,medicine.disease ,Fibrosis ,030104 developmental biology ,Blood pressure ,Endocrinology ,Glucose ,Gene Expression Regulation ,Heart failure ,Heart Function Tests ,Hypertension ,Collagen ,Cardiology and Cardiovascular Medicine ,Heart failure with preserved ejection fraction ,business ,Biomarkers ,medicine.drug - Abstract
To date, there is no established treatment for heart failure with preserved ejection fraction (HFpEF). Dipeptidyl peptidase-IV (DPP-IV) inhibitors reportedly have improved not only diabetes mellitus but also heart failure with systolic dysfunction in experimental models. We investigated the effects of a DPP-IV inhibitor on HFpEF in rats. Dahl salt-sensitive rats were fed either high-salt (high-salt diet (HSD): 8% NaCl) or low-salt diets (0.3% NaCl) from 6.5 weeks of age. They were then treated with or without a DPP-IV inhibitor, vildagliptin (10 mg/kg/day, orally), from 11 weeks of age for 9 weeks and analyzed at the age of 20 weeks. HSD rats mimicked the pathophysiology of HFpEF. There were no differences in heart rate, blood pressure, left ventricular (LV) systolic function, or the extent of LV hypertrophy between HSD rats with or without vildagliptin. However, vildagliptin decreased LV end-diastolic pressure, the most reliable hemodynamic parameter of HFpEF in HSD rats. Vildagliptin also decreased the LV distensibility index, a sensitive marker of LV diastolic function in HSD rats. Vildagliptin decreased the expression of collagen genes in HSD hearts and attenuated LV interstitial fibrosis (HSD with vehicle and vildagliptin, 2.9% vs. 1.9%; P 0.05). Furthermore, vildagliptin administration reduced both plasma renin activity and aldosterone concentrations in HSD rats. A DPP-IV inhibitor, vildagliptin, improved the severity of LV fibrosis, and thus, diastolic dysfunction of HFpEF in Dahl salt-sensitive hypertensive rats. DPP-IV inhibitors are promising medicines for treatment of HFpEF in patients with diabetes mellitus.
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- 2018
122. Cardiovascular Outcomes in Patients with Previous Myocardial Infarction and Mild Diabetes Mellitus Following Treatment with Pioglitazone -Reports from the Japan Working Group for the Assessment Whether Pioglitazone Protects Dm Patients Against Re-Infarction (Ppar Study)
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Kenshi Fujii, Koichi Mizuno, Tohru Kohno, Reimin Sawada, Nobuyuki Ohte, Masatake Fukunami, Kazuo Satake, Masaaki Uematsu, Koichi Tamita, Toshimitsu Hamasaki, Makoto Shimizu, Masafumi Kitakaze, Yorihiko Higashino, Hideo Himeno, Toyoaki Murohara, Hiroshi Suzuki, Takaaki Shiono, Hiroshi Asanuma, Yuji Hashimoto, Shunichi Yoda, Shuntaro Ikeda, Kengo Tsukahara, Makoto Nakahama, Yasuharu Nakama, Yoshiyuki Nagai, Kazuki Fukui, Hiroyuki Takase, Shinji Koba, Masanori Asakura, Jun Takahashi, Yoshihiko Kinoshita, Susumu Fujino, Hiroyasu Uzui, Shoji Yano, Jiyoong Kim, Tsutomu Endo, Hounin Kanaya, Taku Matsubara, Takanori Ookusa, Hideki Hayashi, Mitsuru Tsujimoto, Yasuyuki Maruyama, Motoshi Takeuchi, Tetsuya Ishikawa, Shinji Okubo, Kousei Ueda, and Sumio Mizuno
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medicine.medical_specialty ,business.industry ,Unstable angina ,medicine.medical_treatment ,Percutaneous coronary intervention ,medicine.disease ,Internal medicine ,Diabetes mellitus ,medicine ,Clinical endpoint ,Myocardial infarction ,business ,Pioglitazone ,Stroke ,medicine.drug ,Macrovascular disease - Abstract
Background: Secondary prevention in patients with myocardial infarction (MI) is critically important to prevent ischaemic heart failure and reduce social burden. Pioglitazone improves vascular dysfunction and prevents coronary atherosclerosis, mainly via anti-inflammatory and antiatherogenic effects by enhancing adiponectin production in addition to antihyperglycemic effects, thus suggesting that pioglitazone attenuates cardiovascular events in patients with mild (HbA1c levels < 6·5%) diabetes mellitus (DM). Therefore, we evaluated the effects of pioglitazone on cardiovascular events in patients with both previous MI and mild DM. Methods: In this multicentre, prospective, randomised, open, blinded-endpoint trial of PPAR study, we randomly assigned 630 patients with mild DM with a history of MI to undergo either DM therapy with (pioglitazone group) or without (control group) pioglitazone. DM was diagnosed using the 75-g oral glucose tolerance test, and mild DM was defined if HbA1c level was < 6·5%. The primary endpoint was the composite of cardiovascular death and hospitalisation caused by acute MI, unstable angina, coronary revascularisation (including percutaneous coronary intervention and cardiac bypass surgery), and stroke. HbA1C levels were 5·9 and 5·8% (p = 0.71) at baseline and 6·0 and 5·8% (p < 0.01) at 2 years for the control and pioglitazone groups, respectively. Findings: The primary endpoint was observed in 14·2% and 14·1% patients in the control and pioglitazone groups during two years, respectively; the incidence of MI and stroke was 0·3% and 2·2% and 1·0% and 0·3%, respectively. Post-hoc analyses of the 7-year observation period showed that these trends became clearer. Interpretation: Pioglitazone could not reduce the occurrence of cardiovascular events in patients with mild DM and previous MI. This result contradicts the results of the IRIS trial that pioglitazone decreased cardiovascular events in stroke patients or the results of the PROactive trial that pioglitazone decreased cardiovascular events in patients with moderate DM and macrovascular disease. Funding: The Grants of Japan Heart Foundation for PPAR study. Conflict of Interest: Dr. Asakura reports grants from Acterion Pharmaceutical Japan, grants from Boehringer Ingelheim Japan, Inc., personal fees from Otsuka Pharmaceutical Co., Ltd., personal fees from Sanofi K.K., personal fees from Bayer Yakuhin, Ltd., personal fees from MSD K.K., personal fees from Takeda Pharmaceutical Company Limited., personal fees from ONO PHARMACEUTICAL CO., LTD., personal fees from Mitsubishi Tanabe Pharma Corporation, personal fees from DAIICHI SANKYO COMPANY, LIMITED , personal fees from Pfizer Japan Inc., personal fees from Astellas Amgen Biopharma, outside the submitted work. Dr. Kim has nothing to disclose. Dr. Asanuma reports grants from Japan Heart Foundation, during the conduct of the study; grants from Japan Society For The Promotion Of Science (Grants-in-Aid For Scientific Research), grants from Novartis Pharmaceuticals Corporation, grants from Mitsubishi Tanabe Pharma Corporation, personal fees from Otsuka Pharmaceutical Co,Ltd, personal fees from Kyowa Hakko Kirin Co, Ltd, personal fees from Daiichi Sankyo Company, Limited, outside the submitted work. Dr. Hamasaki has nothing to disclose. Dr. Nakama has nothing to disclose. Dr. Tsukahara reports grants from Japan Heart Foundation, during the conduct of the study. Dr. Higashino reports grants from Japan Heart Foundation, during the conduct of the study. Dr. Ishikawa reports grants from Japan Heart Foundation during the conduct of the study. Dr. Koba reports grants from Japan Heart Foundation during the conduct of the study; grants from Daiichi Sankyo Company, Ltd, personal fees from MSD K.K. outside the submitted work. Ethical Approval Statement: The study was performed following the principles of the Declaration of Helsinki and the Japanese ethical guidelines for clinical research.
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- 2018
123. Abstract 21151: Safety and Feasibility Report of Investigational Therapy With Interleukin-11 Against Acute Myocardial Infarction
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Makiko Maeda, Masaki Nakagawa, Yasuko Owada, Yasukatsu Izumi, Shinichi Nonin, Kenichi Sugioka, Daisaku Nakatani, Shinichi Iwata, Kazuki Mizutani, Satoshi Nishimura, Asahiro Ito, Suwako Fujita, Takashi Daimon, Yoshiki Sawa, Masanori Asakura, Yasushi Fujio, and Minoru Yoshiyama
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Physiology (medical) ,cardiovascular diseases ,Cardiology and Cardiovascular Medicine - Abstract
Introduction: The benefits of vessel recanalization in acute myocardial infarction (AMI) are limited by ischemia/reperfusion (IR) injury. We have reported IL-11, a kind of IL-6 family cytokine, confers resistance to IR injury on cardiomyocytes both in vitro and in vivo and reduces infarct size and improved ventricular function after I/R injury in vivo. Importantly, recombinant human IL-11 (rhIL-11) was clinically used for the prevention of severe thrombocytopenia after chemotherapy under the approval of FDA. Hypothesis: The aim of this study was to evaluate the safety and feasibility of rhIL-11, adjunct to primary percutaneous coronary intervention (PCI) in AMI. Methods: Four patients with STEMI undergoing primary PCI were enrolled based on inclusion criteria, such as culprit lesion of #6 or #7 with TIMI flow grade 0 or 1 on coronary angiography (CAG). Just after diagnosis by CAG, rhIL-11 (6 or 25 μg/kg) was intravenously administered for a period of 3 hours (hr). The primary endpoint were safety and tolerability for 7days after the administration. Serum creatine kinase (CK) was measured pre- and 1, 2.5, 3, 6, 10, 15, 24, 48 hr after injection. Echocardiography was performed pre-, 7days, 3 and 6 months after injection. Results: Just after injection of rhIL-11, PCI was successfully performed and no severe or serious drug adverse events occurred through the observation period in any cases. And they left the hospital without symptoms of heart failure. In addition, no unexpected reduction in left ventricular ejection fraction (LVEF) was observed in the patients treated with rhIL-11 (LVEF, 39.8±8.8 %; CK max , 6906.3±3546 U/L), compared with non-treated internal controls with similar baseline demographics including CK max and LVEF at chronic phase after AMI. Conclusions: Conclusively, we described the four cases of rhIL-11 therapy against STEMI as a novel cytokine therapy for the first time, and this therapy was feasible and well tolerated in AMI. In order to address the efficacy of rhIL-11 therapy, we have been preparing randomized controlled trial to investigate efficacy and safety of rhIL-11 in the patients with STEMI, and the protocol for the trial was approved as advanced medical care by Japanese Ministry of Health, Labour and Welfare last December.
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- 2017
124. Novel Synthesized Radical-Containing Nanoparticles Limit Infarct Size Following Ischemia and Reperfusion in Canine Hearts
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Madoka Ihara, Seiji Takashima, Yoshihiro Asano, Hideyuki Sasaki, Shoji Sanada, Hidezo Mori, Masafumi Kitakaze, Masaru Sugimachi, Yukio Nagasaki, Toru Yoshitomi, Hiroyuki Takahama, Hiroshi Asanuma, Yoshiro Shinozaki, Tetsuo Minamino, Hiroko Takahama, Atsushi Nakano, and Masanori Asakura
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0301 basic medicine ,medicine.medical_specialty ,Cardiotonic Agents ,Ischemia ,Myocardial Infarction ,Myocardial Reperfusion Injury ,030204 cardiovascular system & hematology ,Nitric Oxide ,Nitric oxide ,Cyclic N-Oxides ,03 medical and health sciences ,chemistry.chemical_compound ,Coronary circulation ,0302 clinical medicine ,Dogs ,Internal medicine ,Coronary Circulation ,medicine ,Animals ,Pharmacology (medical) ,Myocardial infarction ,Pharmacology ,Cardioprotection ,Drug Carriers ,business.industry ,General Medicine ,Venous blood ,medicine.disease ,Coronary arteries ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Injections, Intravenous ,Cardiology ,Nanoparticles ,Spin Labels ,Cardiology and Cardiovascular Medicine ,business ,Reperfusion injury - Abstract
Although nitroxyl radicals such as 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) scavenge free radicals, their short half-life and considerable side effects such as systemic hypotension and bradycardia have limited their clinical application. Since a radical-containing nanoparticle (RNP) delivers nitroxyl radicals with a prolonged half-life specific to ischemic hearts, we investigated whether RNPs reduce infarct size without the occurrence of substantial side effects and whether nitric oxide (NO) contributes to the cardioprotective effects of RNPs. The left anterior descending coronary arteries of dogs were occluded for 90 min, followed by reperfusion for 6 h. Either RNPs, micelles (not containing TEMPO) (control), or 4-hydroxy-TEMPO (TEMPOL) was injected into a systemic vein for 5 min before reperfusion. We evaluated the infarct size, myocardial apoptosis, plasma NO levels in coronary venous blood, and the RNP spectra using an electron paramagnetic resonance assay. RNPs reduced infarct size compared with the control group and TEMPOL group (19.5 ± 3.3 vs. 42.2 ± 3.7 vs. 30.2 ± 3.4%). RNPs also reduced myocardial apoptosis compared with the control and TEMPOL group. Coronary venous NO levels increased in the RNP group. In conclusion, the administration of 2,2,6,6-tetramethylpiperidine-1-oxyl as a RNP exerted cardioprotective effects against ischemia and reperfusion injury in canine hearts without exerting unfavorable hemodynamic effects. RNPs may represent a promising new therapy for patients with acute myocardial infarction.
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- 2017
125. Data Mining as a Powerful Tool for Creating Novel Drugs in Cardiovascular Medicine: The Importance of a 'Back-and-Forth Loop' Between Clinical Data and Basic Research
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Takashi Washio, Masafumi Kitakaze, Atsushi Nakano, Seiji Takashima, and Masanori Asakura
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medicine.medical_specialty ,Big data ,Alternative medicine ,MEDLINE ,Bioinformatics ,Medical Records ,Field (computer science) ,Translational Research, Biomedical ,Basic research ,Drug Discovery ,Human Genome Project ,medicine ,Data Mining ,Humans ,Pharmacology (medical) ,Intensive care medicine ,Pharmacology ,business.industry ,Medical record ,Genetic data ,Cardiovascular Agents ,General Medicine ,Clinical trial ,Cardiovascular Diseases ,Cardiology and Cardiovascular Medicine ,business - Abstract
Cardiovascular diseases, which lead to cardiovascular events including death, progress with many deleterious pathophysiological sequels. If a cause-and-effect relationship follows a one-to-one relation, we can focus on a cause to treat an effect, but such a relation cannot be applied in cardiovascular diseases. To identify novel drugs in the cardiovascular field, we generally adopt two different strategies: induction and deduction. In the cardiovascular field, it is difficult to use deduction because cardiovascular diseases are caused by many factors, leading us to use induction. In this method, we consider all clinical data, such as medical records or genetic data, and identify a few candidates. Recent computational and mathematical advances enable us to use data-mining methods to uncover hidden relationships between many parameters and clinical outcomes. However, because these candidates are not identified as promoting or inhibiting factors, or as causal or consequent factors of cardiovascular diseases, we need to test them in basic research, and bring them back to the clinical field to test their efficacy in clinical trials. With such a "back-and-forth loop" between clinical observation and basic research, data-mining methods may provide novel strategies leading to new tools for clinicians, basic findings for researchers, and better outcomes for patients.
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- 2015
126. An interaction between glucagon-like peptide-1 and adenosine contributes to cardioprotection of a dipeptidyl peptidase 4 inhibitor from myocardial ischemia-reperfusion injury
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Hisakazu Kato, Yoshihiro Asano, Yoshihiro Shinozaki, Tetsuo Minamino, Masanori Asakura, Madoka Ihara, Masaru Sugimachi, Hiroshi Asanuma, Hidezo Mori, Masafumi Kitakaze, Satoru Yamazaki, and Naoki Mochizuki
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medicine.medical_specialty ,Adenosine ,Cardiotonic Agents ,Adenosine Deaminase ,Physiology ,Dipeptidyl Peptidase 4 ,Apoptosis ,Myocardial Reperfusion Injury ,Dipeptidyl peptidase-4 inhibitor ,Biology ,Glycogen Synthase Kinase 3 ,Dogs ,Piperidines ,Theophylline ,Glucagon-Like Peptide 1 ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,Cyclic AMP Response Element-Binding Protein ,Extracellular Signal-Regulated MAP Kinases ,Uracil ,Dipeptidyl peptidase-4 ,Cardioprotection ,Dipeptidyl-Peptidase IV Inhibitors ,Glycogen Synthase Kinase 3 beta ,Hemodynamics ,Metabolism ,medicine.disease ,Glucagon-like peptide-1 ,Endocrinology ,Purinergic P1 Receptor Antagonists ,Female ,Cardiology and Cardiovascular Medicine ,Proto-Oncogene Proteins c-akt ,Reperfusion injury ,Protein Binding ,medicine.drug ,Hormone - Abstract
Dipeptidyl peptidase 4 (DPP4) inhibitors suppress the metabolism of the potent antihyperglycemic hormone glucagon-like peptide-1 (GLP-1). DPP4 was recently shown to provide cardioprotection through a reduction of infarct size, but the mechanism for this remains elusive. Known interactions between DPP4 and adenosine deaminase (ADA) suggest an involvement of adenosine signaling in DPP4 inhibitor-mediated cardioprotection. We tested whether the protective mechanism of the DPP4 inhibitor alogliptin against myocardial ischemia-reperfusion injury involves GLP-1- and/or adenosine-dependent signaling in canine hearts. In anesthetized dogs, the coronary artery was occluded for 90 min followed by reperfusion for 6 h. A 4-day pretreatment with alogliptin reduced the infarct size from 43.1 ± 2.5% to 17.1 ± 5.0% without affecting collateral flow and hemodynamic parameters, indicating a potent antinecrotic effect. Alogliptin also suppressed apoptosis as demonstrated by the following analysis: 1) reduction in the Bax-to-Bcl2 ratio; 2) cytochrome c release, 3) an increase in Bad phosphorylation in the cytosolic fraction; and 4) terminal deoxynucleotidyl transferase dUTP nick end labeling assay. This DPP4 inhibitor did not affect blood ADA activity or adenosine concentrations. In contrast, the nonselective adenosine receptor blocker 8-( p-sulfophenyl)theophylline (8SPT) completely blunted the effect of alogliptin. Alogliptin did not affect Erk1/2 phosphorylation, but it did stimulate phosphorylation of Akt, glycogen synthase kinase-3β, and cAMP response element-binding protein (CREB). Only 8SPT prevented alogliptin-induced CREB phosphorylation. In conclusion, the DPP4 inhibitor alogliptin suppresses ischemia-reperfusion injury via adenosine receptor- and CREB-dependent signaling pathways.
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- 2015
127. Higd1a is a positive regulator of cytochrome c oxidase
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Hisakazu Kato, Shinya Yoshikawa, Takaharu Hayashi, Issei Komuro, Tetsuo Minamino, Ken Matsuoka, Yu-ichi Goto, Yasushi Sakata, Takashi Ogura, Hiroshi Aoyama, Masanori Asakura, Masafumi Kitakaze, Seiji Takashima, Kazuaki Takafuji, Osamu Tsukamoto, Kyoko Shinzawa-Itoh, Tomitake Tsukihara, Atsushi Nakano, Hidetaka Kioka, Hiroshi Asanuma, Yasunori Shintani, Yoshihiro Asano, Masahide Hikita, Satoru Yamazaki, and Shuichiro Higo
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Protein Conformation ,macromolecular substances ,Oxidative phosphorylation ,Mitochondrion ,Oxidative Phosphorylation ,Electron Transport Complex IV ,chemistry.chemical_compound ,Adenosine Triphosphate ,Fluorescence Resonance Energy Transfer ,Animals ,Cytochrome c oxidase ,Hypoxia ,Electrochemical gradient ,HIGD1A ,Multidisciplinary ,ATP synthase ,biology ,Biological Sciences ,Hypoxia-Inducible Factor 1, alpha Subunit ,Mitochondria ,Heme A ,chemistry ,Biochemistry ,biology.protein ,Cattle ,Adenosine triphosphate - Abstract
Cytochrome c oxidase (CcO) is the only enzyme that uses oxygen to produce a proton gradient for ATP production during mitochondrial oxidative phosphorylation. Although CcO activity increases in response to hypoxia, the underlying regulatory mechanism remains elusive. By screening for hypoxia-inducible genes in cardiomyocytes, we identified hypoxia inducible domain family, member 1A (Higd1a) as a positive regulator of CcO. Recombinant Higd1a directly integrated into highly purified CcO and increased its activity. Resonance Raman analysis revealed that Higd1a caused structural changes around heme a, the active center that drives the proton pump. Using a mitochondria-targeted ATP biosensor, we showed that knockdown of endogenous Higd1a reduced oxygen consumption and subsequent mitochondrial ATP synthesis, leading to increased cell death in response to hypoxia; all of these phenotypes were rescued by exogenous Higd1a. These results suggest that Higd1a is a previously unidentified regulatory component of CcO, and represents a therapeutic target for diseases associated with reduced CcO activity.
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- 2015
128. Rationale and Design of the Double-Blind, Randomized, Placebo-Controlled Multicenter Trial on Efficacy of Early Initiation of Eplerenone Treatment in Patients with Acute Heart Failure (EARLIER)
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Youichi Kobayashi, Atsushi Hirayakma, Kuniya Asai, Hiroyuki Uesaka, Ken-ichi Hirata, Shin-ichi Momomura, Masafumi Kitakaze, Tsutomu Yoshikawa, Kazuo Kimura, Akira Yamashina, Yoshihisa Nakagawa, Yasuhiro Satoh, Satoshi Yasuda, Masanori Asakura, Haruko Yamamoto, Takahisa Yamada, Akihisa Hanatani, study coordinators, Akiko Kada, Yoshihiko Saito, and Yutaro Nishi
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Adult ,Male ,medicine.medical_specialty ,Hemodynamics ,Spironolactone ,Placebo ,Young Adult ,chemistry.chemical_compound ,Clinical Protocols ,Double-Blind Method ,Early Medical Intervention ,Multicenter trial ,Internal medicine ,Humans ,Medicine ,Pharmacology (medical) ,In patient ,Mineralocorticoid Receptor Antagonists ,Heart Failure ,Pharmacology ,Aldosterone ,business.industry ,Antagonist ,General Medicine ,medicine.disease ,Eplerenone ,chemistry ,Heart failure ,Acute Disease ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
Aldosterone is one of the major factors to cause organ damage during an acute phase of heart failure (HF), and many reports have demonstrated that patients with acute decompensated HF (ADHF) have high blood aldosterone concentrations, and the high aldosterone concentrations predict poor prognosis in patients with HF. These findings suggest that eplerenone, an antagonist of aldosterone receptors may provide a new concept and strategy for the treatment of ADHF, protecting the heart and other organs during chronic phases, depending on the restoration of hemodynamic abnormalities.EARLIER is an event-driven clinical trial with an estimated enrolment of 300 patients hospitalized with ADHF with reduced left ventricular ejection fraction. ADHF includes ischemic or non-ischemic HF, and patients can be enrolled within 72 h after the visit to the hospital. We randomize the patients taking standard therapies for ADHF to the eplerenone and placebo groups. Eplerenone, either 25 or 50 mg, is administered for 6 months in the eplerenone group, and the corresponding placebo is administered in the placebo group on top of the standard care. We set the primary endpoint as the incidence of the composite endpoint (cardiac death or first re-hospitalization due to cardiac disease) 6 months after the enrollment, and also check the quality of life, i.e., exercise capacity and safety features of eplerenone.EARLIER is a clinical trial of eplerenone targeting ADHF and also the first multicenter investigator-initiated phase III trial in the cardiovascular field in Japan, funded by the Japanese government.
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- 2015
129. Pathophysiological impact of serum fibroblast growth factor 23 in patients with nonischemic cardiac disease and early chronic kidney disease
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Hiroshi Asanuma, Toshihisa Anzai, Takahiro Ohara, Masafumi Kitakaze, Miki Imazu, Yasuo Sugano, Takuya Hasegawa, Hiroyuki Takahama, Akira Funada, Hideaki Kanzaki, and Masanori Asakura
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Adult ,Male ,Fibroblast growth factor 23 ,medicine.medical_specialty ,Systole ,Physiology ,Kaplan-Meier Estimate ,Disease ,Fibroblast growth factor ,Severity of Illness Index ,Ventricular Function, Left ,Predictive Value of Tests ,Risk Factors ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,In patient ,Prospective Studies ,Renal Insufficiency, Chronic ,Aldosterone ,Aged ,Heart Failure ,business.industry ,Stroke Volume ,Middle Aged ,Prognosis ,medicine.disease ,Pathophysiology ,Up-Regulation ,Fibroblast Growth Factors ,Hospitalization ,Fibroblast Growth Factor-23 ,Cross-Sectional Studies ,Endocrinology ,Heart failure ,Multivariate Analysis ,Linear Models ,Female ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers ,Glomerular Filtration Rate ,Kidney disease - Abstract
Although the important role of fibroblast growth factor (FGF)23 on cardiac remodeling has been suggested in advanced chronic kidney disease (CKD), little is known about serum (s)FGF23 levels in patients with heart failure (HF) due to nonischemic cardiac disease (NICD) and early CKD. The present study aimed to investigate sFGF23 levels in NICD patients and identify the responsible factors for the elevation of sFGF23 levels. We prospectively measured sFGF23 levels in consecutive hospitalized NICD patients with early CKD (estimated glomerular filtration rate ≥ 40 ml·min−1·1.73 m−2) and analyzed the data of both echocardiography and right heart catheterization. Of the 156 NICD patients (estimated glomerular filtration rate range: 41–128 ml·min−1·1.73 m−2), the most severe HF symptom (New York Heart Association class III-IV, 53% vs. 33%, P = 0.015) was found in the above median sFGF23 (39.1 pg/ml) group compared with the below median sFGF23 group. sFGF23 levels were higher in patients with HF hospitalization history compared with those without HF [median: 46.8 (interquartile range: 38.8–62.7) vs. 34.7 (interquartile range: 29.6–42.4) pg/ml, P < 0.0001]. In the multivariate analysis, HF hospitalization was independently related to elevated sFGF23 levels ( P = 0.022). Both systolic dysfunction and high plasma aldosterone concentration were identified as predictors of high sFGF23 levels ( P < 0.05). Among the neurohormonal parameters, elevated sFGF23 levels were the only factor to predict a declining left ventricular ejection fraction ( P = 0.001). These findings suggest that the progression of HF per se contributes to the elevation of sFGF23 levels even in the early stages of CKD, which leads to further myocardial dysfunction, potentially creating a vicious cycle.
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- 2014
130. Clinical benefit of drugs targeting mitochondrial function as an adjunct to reperfusion in ST-segment elevation myocardial infarction: A meta-analysis of randomized clinical trials
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Michel Ovize, Dana Dawson, A. Michael Lincoff, Marcello Galvani, Paolo Pinton, Giampaolo Morciano, Filippo Ottani, Roberto Ferrari, Dan Atar, Gianluca Campo, Daniel A. Jones, Hideki Ishii, Michael P. Frenneaux, Simone Biscaglia, Rita Pavasini, Jacob Lønborg, Masanori Asakura, C. Michael Gibson, Amrita Ahluwalia, Brandon J. Neil, Masafumi Kitakaze, Borja Ibanez, Thomas Engstrøm, Giampaolo Cerisano, Azienda Ospedaliero [Ferrara, Italy], University of Ferrara [Ferrara], Cleveland Clinic, Harvard Medical School [Boston] (HMS), Rigshospitalet [Copenhagen], William Harvey Research Institute, Barts and the London Medical School, Nagoya University Graduate School of Medicine [Japon], School of Medicine, University of East Anglia, Norwich, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Oslo University Hospital [Oslo], Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Careggi Hospital, University of Aberdeen, Maria Cecilia Hospital [Cotignola], Università degli Studi di Ferrara (UniFE), Copenhagen University Hospital, Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National de la Recherche Agronomique (INRA)
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0301 basic medicine ,medicine.medical_specialty ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Myocardial Reperfusion ,030204 cardiovascular system & hematology ,Placebo ,NO ,law.invention ,03 medical and health sciences ,Drug Delivery Systems ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,Humans ,Medicine ,Myocardial infarction ,Mortality ,Adverse effect ,ComputingMilieux_MISCELLANEOUS ,Randomized Controlled Trials as Topic ,Ejection fraction ,business.industry ,Primary percutaneous coronary intervention ,Percutaneous coronary intervention ,Cardiovascular Agents ,Odds ratio ,medicine.disease ,Mitochondria ,3. Good health ,Reperfusion injury ,ST-segment elevation myocardial infarction ,Treatment Outcome ,030104 developmental biology ,Conventional PCI ,Cardiology ,ST Elevation Myocardial Infarction ,Mitochondrial function ,Cardiology and Cardiovascular Medicine ,business - Abstract
Aims To perform a systematic review and meta-analysis of randomized clinical trials (RCT) comparing the effectiveness of drugs targeting mitochondrial function vs. placebo in patients with ST-segment elevation myocardial infarction (STEMI) undergoing mechanical coronary reperfusion. Methods Inclusion criteria: RCTs enrolling STEMI patients treated with primary percutaneous coronary intervention (PCI) and comparing drugs targeting mitochondrial function vs. placebo. Odds ratios (OR) were computed from individual studies and pooled with random-effect meta-analysis. Results Fifteen studies were identified involving 5680 patients. When compared with placebo, drugs targeting mitochondrial component/pathway were not associated with significant reduction of cardiovascular and all-cause mortality (OR 0.9, 95% CI 0.7–1.17 and OR 0.92, 95% CI 0.69–1.23, respectively). However, these agents significantly reduced hospital admission for heart failure (HF) (OR 0.64; 95% CI 0.45–0.92) and increased left ventricular ejection fraction (LVEF) (OR 1.44; 95% CI 1.15–1.82). After analysis for subgroups according to the mechanism of action, drugs with direct/selective action did not reduce any outcome. Conversely, those with indirect/unspecific action showed a significant effect on cardiovascular mortality (0.65, 95% CI 0.46–0.92), all-cause mortality (OR 0.69, 95% CI 0.52–0.92), hospital readmission for HF (OR 0.41, 95% CI 0.28–0.6) and LVEF (OR 1.49, 95% CI 1.09–2.05). Conclusions Administration of drugs targeting mitochondrial function in STEMI patients undergoing primary PCI appear to have no effect on mortality, but may reduce hospital readmission for HF. The drugs with a broad-spectrum mechanism of action seem to be more effective in reducing adverse events.
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- 2017
131. Interatrial septal motion as a novel index to predict left atrial pressure
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Kenki Ashida, Akiko Goda, Masanori Asakura, Takanao Mine, Satoshi Takahashi, Kumiko Masai, Masaharu Ishihara, Hideyuki Kishima, and Tohru Masuyama
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Male ,medicine.medical_specialty ,medicine.medical_treatment ,Atrial Pressure ,Catheter ablation ,Atrial Function, Right ,030204 cardiovascular system & hematology ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Rhythm ,law ,Internal medicine ,Atrial Fibrillation ,medicine ,Humans ,Sinus rhythm ,cardiovascular diseases ,030212 general & internal medicine ,Heart Atria ,Aged ,Retrospective Studies ,Atrial Septum ,business.industry ,Central venous pressure ,Atrial fibrillation ,medicine.disease ,Prognosis ,Cardiac surgery ,Pressure measurement ,Echocardiography ,Preoperative Period ,cardiovascular system ,Cardiology ,Catheter Ablation ,Female ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies - Abstract
We investigated whether the interatrial septal (IAS) motion of each heartbeat which is observed by transesophageal echocardiography reflects left atrial pressure (LAP) in patients with atrial fibrillation (AF). We studied 100 patients (70 males, age 67 ± 9 years) who underwent catheter ablation for AF. The amplitude of IAS motion was measured using M-mode and averaged for five cardiac cycles. Left and right atrial pressures, the left to right atrial pressure gradient were directly measured during the catheter ablation. In patients with sinus rhythm during measurement, elevated mean LAP, larger maximum left to right atrial pressure gradient, and greater left atrial emptying fraction were associated with IAS motion. The optimal cut-off value of the IAS motion for predicting high LAP (mean LAP > 15 mmHg) was 8.5 mm (sensitivity 100%, specificity 70.1%) in patients with sinus rhythm during pressure measurement. In addition, all patients were divided into 6 groups based on rhythm during measurement and cutoff value of IAS motion. In patients with sinus rhythm during measurement, low IAS motion group had a highest prevalence of elevated LAP compared with high IAS motion group (64 vs. 0%, P
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- 2017
132. Does Treatment of Impaired Glucose Tolerance Improve Cardiovascular Outcomes in Patients with Previous Myocardial Infarction?
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Yoshiyuki Nagai, Yoshihiko Kinoshita, Sumio Mizuno, Shunichi Yoda, Takahisa Yamada, Isao Morii, Masashi Fujita, Yasuyuki Maruyama, Takahiro Muroya, Hiroshi Suzuki, Reimin Sawada, Takayoshi Yamanouchi, Abc investigators, Susumu Fujino, Mitsuru Tsujimoto, Masataka Sata, Kazuki Fukui, Yasuharu Nakama, Takanori Ohkusa, Toyoaki Murohara, Yuji Hashimoto, Hiroyuki Takase, Tetsuya Ishikawa, Hajime Yamaguchi, Nobuyuki Ohte, Masafumi Kitakaze, Hideki Hayashi, Shuntaro Ikeda, Kazuo Satake, Hideo Himeno, Tomohiko Shigemasa, Koichi Tamita, Jiyoong Kim, Hiroyasu Uzui, Yorihiko Higashino, Masanori Asakura, Tsutomu Endo, Tetsuro Ueda, Makoto Nakahama, Tatsuya Nunohiro, Osamu Doi, Toshimitsu Hamasaki, Takaaki Shiono, Kengo Tsukahara, Tohru Kohno, Makoto Shimizu, Satoru Sakagami, Yukiko Morita, Shinji Koba, Yoshikazu Hiasa, Hiroshi Asanuma, and Jitsuo Higaki
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Male ,medicine.medical_specialty ,medicine.medical_treatment ,Myocardial Infarction ,Kaplan-Meier Estimate ,030204 cardiovascular system & hematology ,Impaired glucose tolerance ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Internal medicine ,Voglibose ,Glucose Intolerance ,Clinical endpoint ,Secondary Prevention ,Medicine ,Humans ,Hypoglycemic Agents ,Pharmacology (medical) ,Glycoside Hydrolase Inhibitors ,030212 general & internal medicine ,Myocardial infarction ,Prospective Studies ,Prospective cohort study ,Aged ,Pharmacology ,business.industry ,Unstable angina ,Percutaneous coronary intervention ,General Medicine ,Middle Aged ,medicine.disease ,Discontinuation ,Treatment Outcome ,Cardiovascular Diseases ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,Inositol ,medicine.drug - Abstract
We evaluated the effects of an alpha-glucosidase inhibitor, voglibose, on cardiovascular events in patients with a previous myocardial infarction (MI) and impaired glucose tolerance (IGT). This prospective, randomized, open, blinded-endpoint study was conducted in 112 hospitals and clinics in Japan in 3000 subjects with both previous MI and IGT receiving voglibose (0.6 mg/day, n = 424) or no drugs (n = 435) for 2 years. The Data and Safety Monitoring Board (DSMB) recommended discontinuation of the study in June 2012 after an interim analysis when the outcomes of 859 subjects were obtained. The primary endpoint was cardiovascular events including cardiovascular death, nonfatal MI, nonfatal unstable angina, nonfatal stroke, and percutaneous coronary intervention/coronary artery bypass graft. Secondary endpoints included individual components of the primary endpoint in addition to all-cause mortality and hospitalization due to heart failure. The age, ratio of males, and HbA1C were 65 vs. 65 years, 86 vs. 87%, and 5.6 vs. 5.5% in the groups with and without voglibose, respectively. Voglibose improved IGT; however, Kaplan–Meier analysis showed no significant between-group difference with respect to cardiovascular events [12.5% with voglibose vs. 10.1% without voglibose for the primary endpoint (95% confidence interval, 0.82–1.86)]; there were no significant differences in secondary endpoints. Although voglibose effectively treated IGT, no additional benefits for cardiovascular events in patients with previous MI and IGT were observed. Voglibose may not be a contributing therapy to the secondary prevention in patients with MI and IGT. Clinicaltrials.gov number: NCT00212017
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- 2017
133. P5283Differential prognostic impact of anemia in male and female patients with heart failure with preserved ejection fraction: analysis of Japanese Heart Failure Syndrome with Preserved Ejection Fraction
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Toshiyuki Nagai, Tomotaka Ando, Yoshihiko Saito, Masataka Sugahara, Toshihisa Anzai, Yoshiro Naito, Tohru Masuyama, Keisuke Okuno, Tsutomu Yoshikawa, and Masanori Asakura
- Subjects
medicine.medical_specialty ,Ejection fraction ,business.industry ,Anemia ,Internal medicine ,Heart failure ,Female patient ,medicine ,Cardiology ,Cardiology and Cardiovascular Medicine ,Heart failure with preserved ejection fraction ,medicine.disease ,business - Published
- 2017
134. Effect of Mitral Valve Surgery in Patients With Dilated Cardiomyopathy and Severe Functional Mitral Regurgitation
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Masanori Asakura, Hiroyuki Takahama, Hideaki Kanzaki, Yasuo Sugano, Takahiro Ohara, Makoto Amaki, Tomoyuki Fujita, Masafumi Kitakaze, Junjiro Kobayashi, Toshihisa Anzai, Seiji Takashio, Takuya Hasegawa, and Hyemoon Chung
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Adult ,Cardiomyopathy, Dilated ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Mitral valve ,Medicine ,Humans ,030212 general & internal medicine ,Ventricular remodeling ,Aged ,Proportional Hazards Models ,business.industry ,Proportional hazards model ,Hazard ratio ,Mitral Valve Insufficiency ,Dilated cardiomyopathy ,General Medicine ,Middle Aged ,medicine.disease ,Confidence interval ,medicine.anatomical_structure ,Treatment Outcome ,Ventricular assist device ,Heart failure ,Cardiology ,Mitral Valve ,Female ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies - Abstract
Background Surgical treatment of functional mitral regurgitation (FMR) improves ventricular remodeling in patients with dilated cardiomyopathy (DCM). However, it is unclear whether surgical treatment improves long-term outcomes. We investigated the effects of mitral valve (MV) surgery in patients with DCM and FMR.Methods and Results:Of 525 patients with DCM hospitalized due to heart failure between January 1996 and September 2014, 70 who had severe FMR despite receiving optimal medical therapy were enrolled in the study. Of these patients, 16 underwent surgery for FMR (surgery group; repair=14, replacement=2); the remaining 54 who refused or decided not to undergo surgery were classified as the medication group. There were no differences in age, sex, medication, or echocardiographic parameters between the 2 groups (P>0.05). During the mean follow-up period of 53.6±43.6 months, the occurrence of clinical outcomes (i.e., all-cause death or left ventricular assist device implantation) was 54.3%; the occurrence of clinical outcomes was lower in the surgery group (P=0.008, log-rank test). Multivariate Cox regression analysis using clinical data revealed that MV surgery (hazard ratio [HR] 0.257, 95% confidence interval [CI] 0.103-0.640; P=0.004) and diabetes mellitus (HR 2.924, 95% CI 1.243-6.876; P=0.014) were independent predictors of clinical outcomes after adjusting for age and sex. Conclusions Surgery for severe FMR provides better long-term outcomes in patients with DCM.
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- 2017
135. Regulators of K_2 of Hypergeometric Fibrations
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Masanori Asakura
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Pure mathematics ,Algebra and Number Theory ,Conjecture ,Mathematics::Classical Analysis and ODEs ,Hypergeometric functions ,Hypergeometric distribution ,Elliptic curve ,Mathematics - Algebraic Geometry ,Mathematics::Algebraic Geometry ,Number theory ,Mathematics::K-Theory and Homology ,Regulators ,FOS: Mathematics ,L-function ,Hypergeometric function ,Periods ,Value (mathematics) ,Algebraic Geometry (math.AG) ,Mathematics ,14D07, 19F27, 33C20 (primary), 11G15, 14K22 (secondary) - Abstract
We discuss Beilinson's regulator on K_2 of certain fibrations of algebraic varieties which we call the hypergeomtric fibrations. The main result is to describe regulators via the hypergeometric functions 3F2 or 4F3. We also discuss the Beilinson conjecture on the special values of L-functions., 25 pages
- Published
- 2017
136. Carperitide induces coronary vasodilation and limits infarct size in canine ischemic hearts: role of NO
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Hidezo Mori, Jiyoong Kim, Yoshiro Shinozaki, Hiroshi Asanuma, Yoshihiro Asano, Tetsuo Minamino, Masafumi Kitakaze, Masanori Asakura, Seiji Takashima, and Shoji Sanada
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medicine.medical_specialty ,Physiology ,Vasodilator Agents ,Myocardial Infarction ,Myocardial Ischemia ,Myocardial Reperfusion Injury ,Vasodilation ,Nitric Oxide ,Dogs ,Coronary Circulation ,Internal medicine ,Cyclic AMP ,Internal Medicine ,medicine ,Animals ,cardiovascular diseases ,business.industry ,Myocardium ,Infarct size ,Coronary Vessels ,Myocardial Contraction ,Anesthesia ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,Receptors, Atrial Natriuretic Factor ,Atrial Natriuretic Factor - Abstract
Carperitide is effective for heart failure (HF) owing to its diuretic and vasodilatory effects. This recombinant peptide may also have direct cardioprotective effects because carperitide reduces the severity of heart failure and limits infarct size. Because coronary vasodilation is an important cardioprotective treatment modality, we investigated whether carperitide increased coronary blood flow (CBF) and improved myocardial metabolic and contractile dysfunction during ischemia in canine hearts. We also tested whether carperitide is directly responsible for limiting the infarct size. We infused carperitide at 0.025-0.2 μg kg(-1) min(-1) into the canine coronary artery. A minimum dose of 0.1 μg kg(-1) min(-1) was required to obtain maximal vasodilation. To test the effects of carperitide on ischemic hearts, we reduced perfusion pressure in the left anterior descending coronary artery such that CBF decreased to one-third of the baseline value. At 10 min after carperitide was infused at a dose of 0.1 μg kg(-1) min(-1), we observed increases in CBF, fractional shortening (FS) and pH levels in coronary venous blood without concomitant increases in cardiac nitric oxide (NO) levels; these changes were attenuated using either the atrial natriuretic peptide receptor antagonist HS-142-1 or the NO synthase inhibitor L(ω)-nitroarginine methyl ester (L-NAME). Cyclic guanosine monophosphate (GMP) levels in the coronary artery were elevated in response to carperitide that also limited the infarct size after 90 min of ischemia and subsequent reperfusion. Again, these effects were blunted by L-NAME. Carperitide increases CBF, reduces myocardial contractile and metabolic dysfunction and limits infarct size. In addition, NO is necessary for carperitide-induced vasodilation and cardioprotection in ischemic hearts.
- Published
- 2014
137. Does the pathophysiology of heart failure prime the incidence of cancer?
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Toshimitsu Hamasaki, Hideaki Kanzaki, Masafumi Kitakaze, Naoki Mochizuki, Toshihisa Anzai, Makoto Amaki, Masanori Asakura, Takuya Hasegawa, Hiroyuki Takahama, and Mari Sakamoto
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Male ,medicine.medical_specialty ,Physiology ,White coat hypertension ,030204 cardiovascular system & hematology ,Prehypertension ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Internal medicine ,Neoplasms ,Internal Medicine ,Prevalence ,Medicine ,Humans ,cardiovascular diseases ,Intensive care medicine ,health care economics and organizations ,Aged ,Retrospective Studies ,Heart Failure ,business.industry ,Incidence (epidemiology) ,Cancer ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Comorbidity ,humanities ,030220 oncology & carcinogenesis ,Heart failure ,Cohort ,cardiovascular system ,Female ,Cardiology and Cardiovascular Medicine ,business ,circulatory and respiratory physiology - Abstract
Both chronic heart failure (CHF) and cancer are among the most frequent causes of death in developed countries. Given that CHF activates neurohumoral factors, such as cytokines, the pathophysiology of CHF could prime the onset or progression of cancer. We consecutively enrolled 5238 patients with CHF who had been hospitalized in the Department of Cardiovascular Medicine in our institute between 2001 and 2013. We followed these patients until April 2015. We examined the cohort of patients from our hospital and compared it with a control cohort derived from the 2008 cancer database 'Monitoring of Cancer Incidence in Japan' from the National Cancer Center, Japan. The incidence of cancer in CHF patients (198 cases out of the 5238 patients) was approximately four times higher than that in control patients (2.27% vs 0.59%, P
- Published
- 2016
138. Reply to 'The Effects of Tranilast on Cardiomyopathy in Becker Muscular Dystrophy Requires Profound Cardiac and Neurologic Evaluations'
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Masanori Asakura, Yuko Iwata, and Tsuyoshi Matsumura
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muscular dystrophy ,Cardiomyopathy, Dilated ,0301 basic medicine ,medicine.medical_specialty ,Tranilast ,Cardiomyopathy ,member 2 (TRPV2) ,030105 genetics & heredity ,03 medical and health sciences ,cardioprotective therapy ,subfamily V ,Internal medicine ,Internal Medicine ,medicine ,Humans ,ortho-Aminobenzoates ,Muscular dystrophy ,Letters to the Editor ,transient receptor potential cation channel ,business.industry ,Heart ,General Medicine ,tranilast ,medicine.disease ,Muscular Dystrophy, Duchenne ,Cardiology ,Cardiomyopathies ,business ,cardiomyopathy ,medicine.drug - Published
- 2018
139. Explicit logarithmic formulas of special values of hypergeometric functions 3F2
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Toshifumi Yabu and Masanori Asakura
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Pure mathematics ,Logarithm ,Applied Mathematics ,General Mathematics ,010102 general mathematics ,Complex multiplication ,Special values ,14D07, 19F27, 33C20, 11G15, 14K22 ,01 natural sciences ,010101 applied mathematics ,Mathematics - Algebraic Geometry ,FOS: Mathematics ,0101 mathematics ,Hypergeometric function ,Algebraic Geometry (math.AG) ,Mathematics - Abstract
In a joint paper [4] by Otsubo, Terasoma and the first author, we proved that the special value 3F2(a,b,q;a+b,q;1) of the generalized hypergeometric function is a linear combination of log of algebraic numbers if the triplet (a,b,q) of rational numbers satisfies a certain numerical condition. However there remains a question how to obtain explicit descriptions of the values. In this paper, we give a method to do this, which is a further development of the technique in [4]., Comment: 22pages, To appear in Communications in Contemporary Mathematics
- Published
- 2019
140. TRANSFERRIN RECEPTOR 1 HETEROZYGOUS DELETED MICE DID NOT AFFECT BLOOD PRESSURE IN THE DEVELOPMENT OF DIABETIC MELLITUS
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Masanori Asakura, Masaharu Ishihara, Yoshiro Naito, Seiki Yasumura, Keisuke Okuno, and Yuki Matsumoto
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medicine.medical_specialty ,Endocrinology ,Blood pressure ,business.industry ,Internal medicine ,Diabetic mellitus ,medicine ,Transferrin receptor ,Cardiology and Cardiovascular Medicine ,Affect (psychology) ,business - Published
- 2019
141. Evaluation of intramitochondrial ATP levels identifies G0/G1 switch gene 2 as a positive regulator of oxidative phosphorylation
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Takashi Matsuzaki, Hidetaka Kioka, Yasunori Shintani, Masasuke Yoshida, Hiroyuki Noji, Masafumi Kitakaze, Kazuaki Takafuji, Hisakazu Kato, Osamu Tsukamoto, Atsushi Nakano, Hiroshi Asanuma, Issei Komuro, Tetsuo Minamino, Makoto Fujikawa, Toshiharu Suzuki, Masanori Asakura, Hiromi Imamura, Yoshihiro Asano, Seiji Takashima, Satoru Yamazaki, and Shuichiro Higo
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Time Factors ,Cell Survival ,Regulator ,Cell Cycle Proteins ,Biosensing Techniques ,Oxidative phosphorylation ,Biology ,Mitochondrion ,Resting Phase, Cell Cycle ,Oxidative Phosphorylation ,Mice ,chemistry.chemical_compound ,Adenosine Triphosphate ,Oxygen Consumption ,Live cell imaging ,Animals ,Humans ,Myocytes, Cardiac ,Phosphorylation ,Rats, Wistar ,Oligonucleotide Array Sequence Analysis ,Microscopy, Confocal ,Multidisciplinary ,ATP synthase ,HEK 293 cells ,G1 Phase ,Biological Sciences ,Recombinant Proteins ,Mitochondria ,Rats ,Cell biology ,HEK293 Cells ,chemistry ,biology.protein ,Cattle ,Oligomycins ,Adenosine triphosphate ,Genes, Switch ,HeLa Cells - Abstract
The oxidative phosphorylation (OXPHOS) system generates most of the ATP in respiring cells. ATP-depleting conditions, such as hypoxia, trigger responses that promote ATP production. However, how OXPHOS is regulated during hypoxia has yet to be elucidated. In this study, selective measurement of intramitochondrial ATP levels identified the hypoxia-inducible protein G0/G1 switch gene 2 (G0s2) as a positive regulator of OXPHOS. A mitochondria-targeted, FRET-based ATP biosensor enabled us to assess OXPHOS activity in living cells. Mitochondria-targeted, FRET-based ATP biosensor and ATP production assay in a semiintact cell system revealed that G0s2 increases mitochondrial ATP production. The expression of G0s2 was rapidly and transiently induced by hypoxic stimuli, and G0s2 interacts with OXPHOS complex V (FoF1-ATP synthase). Furthermore, physiological enhancement of G0s2 expression prevented cells from ATP depletion and induced a cellular tolerance for hypoxic stress. These results show that G0s2 positively regulates OXPHOS activity by interacting with FoF1-ATP synthase, which causes an increase in ATP production in response to hypoxic stress and protects cells from a critical energy crisis. These findings contribute to the understanding of a unique stress response to energy depletion. Additionally, this study shows the importance of assessing intramitochondrial ATP levels to evaluate OXPHOS activity in living cells.
- Published
- 2013
142. Sarcomere Gene Mutations Are Associated With Increased Cardiovascular Events in Left Ventricular Hypertrophy
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Shintaro Kinugawa, Masa-aki Kawashiri, Ryuichiro Anan, Chuwa Tei, Shigeki Kobayashi, Yoshinori Doi, Masafumi Yano, Hidekazu Ino, Hiroyuki Tsutsui, Toru Kubo, Kenshi Hayashi, Masafumi Kitakaze, Issei Komuro, Noboru Fujino, Tetsuo Konno, Masakazu Yamagishi, Takashi Fujita, and Masanori Asakura
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Fibrillation ,medicine.medical_specialty ,business.industry ,Hypertrophic cardiomyopathy ,Atrial fibrillation ,Gene mutation ,medicine.disease ,Left ventricular hypertrophy ,Ventricular tachycardia ,Hypertensive heart disease ,Heart failure ,Internal medicine ,medicine ,Cardiology ,cardiovascular diseases ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Abstract
Objectives This study investigated the occurrence of cardiovascular events in patients with hypertensive heart disease (HHD) or hypertrophic cardiomyopathy (HCM) with or without sarcomere gene mutations. Background Although HHD and HCM are associated with left ventricular hypertrophy (LVH), few data exist regarding the difference in prognosis between them. Methods We enrolled 256 patients with LVH (>13 mm) screened for sarcomere gene mutations. We divided them into 3 groups: the first had HHD without sarcomere gene mutations (group H), the second had sarcomere gene mutations (group G), and the third had neither sarcomere gene mutations nor HHD (group NG). We compared the occurrence of sudden cardiac death, ventricular tachycardia/fibrillation, admission for heart failure, and atrial fibrillation for 1 year. Results Group G (n = 78, 36 men; mean age, 53.4 years) experienced more total cardiovascular events than group H (n = 45, 32 men; mean age, 67.4 years) (p = 0.042) after adjustments for age and sex, although there was no significant difference in total cardiovascular events between groups H and NG (n = 98, 66 men; mean age, 62.0 years). With Kaplan-Meier analysis, group G exhibited a significantly higher incidence of admission for heart failure (p = 0.017) and atrial fibrillation (p = 0.045) than group H in those 50 years of age and older. Additionally, there was a significant difference in total cardiovascular events between groups G and NG (p = 0.021). Conclusions These results demonstrate that HCM with sarcomere gene mutations can be associated with increased cardiovascular events compared with HHD or HCM without sarcomere gene mutations.
- Published
- 2013
143. Dipeptidyl-peptidase IV inhibition improves pathophysiology of heart failure and increases survival rate in pressure-overloaded mice
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Shin Ito, Kyung-Duk Min, Satoru Yamazaki, Hatsue Ishibashi-Ueda, Masafumi Kitakaze, Shoji Sanada, Hiroshi Asanuma, Kazuhiro Shindo, Yoshihiro Asano, Yulin Liao, Yi Yan, Seiji Takashima, Ayako Takahashi, Tetsuo Minamino, Masanori Asakura, and Naoki Mochizuki
- Subjects
Male ,medicine.medical_specialty ,Pyrrolidines ,Survival ,Physiology ,Blotting, Western ,Incretin ,Adamantane ,Apoptosis ,Blood Pressure ,Enzyme-Linked Immunosorbent Assay ,Real-Time Polymerase Chain Reaction ,Impaired glucose tolerance ,Electrocardiography ,Mice ,Glucagon-Like Peptide 1 ,Heart Rate ,Fibrosis ,Physiology (medical) ,Diabetes mellitus ,Internal medicine ,Nitriles ,In Situ Nick-End Labeling ,medicine ,Animals ,Vildagliptin ,Heart Failure ,Cardioprotection ,Dipeptidyl-Peptidase IV Inhibitors ,Glucose tolerance test ,medicine.diagnostic_test ,business.industry ,Hemodynamics ,Organ Size ,Glucose Tolerance Test ,medicine.disease ,Immunohistochemistry ,Mice, Inbred C57BL ,stomatognathic diseases ,Endocrinology ,Heart failure ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
Incretin hormones, including glucagon-like peptide-1 (GLP-1), a target for diabetes mellitus (DM) treatment, are associated with cardioprotection. As dipeptidyl-peptidase IV (DPP-IV) inhibition increases plasma GLP-1 levels in vivo, we investigated the cardioprotective effects of the DPP-IV inhibitor vildagliptin in a murine heart failure (HF) model. We induced transverse aortic constriction (TAC) in C57BL/6J mice, simulating pressure-overloaded cardiac hypertrophy and HF. TAC or sham-operated mice were treated with or without vildagliptin. An intraperitoneal glucose tolerance test revealed that blood glucose levels were higher in the TAC than in sham-operated mice, and these levels improved with vildagliptin administration in both groups. Vildagliptin increased plasma GLP-1 levels in the TAC mice and ameliorated TAC-induced left ventricular enlargement and dysfunction. Vildagliptin palliated both myocardial apoptosis and fibrosis in TAC mice, demonstrated by histological, gene and protein expression analyses, and improved survival rate on day 28 (TAC with vildagliptin, 67.5%; TAC without vildagliptin, 41.5%; P < 0.05). Vildagliptin improved cardiac dysfunction and overall survival in the TAC mice, both by improving impaired glucose tolerance and by increasing GLP-1 levels. DPP-IV inhibitors represent a candidate treatment for HF patients with or without DM.
- Published
- 2013
144. Direct comparison of the diagnostic capability of cardiac magnetic resonance and endomyocardial biopsy in patients with heart failure
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Takuya Hasegawa, Masanori Asakura, Hatsue Ishibashi-Ueda, Makoto Amaki, Naoaki Yamada, Masafumi Kitakaze, Akemi Yoshida, Hideaki Kanzaki, and Hiroyuki Takahama
- Subjects
Adult ,Cardiomyopathy, Dilated ,Gadolinium DTPA ,Male ,medicine.medical_specialty ,Adolescent ,Sarcoidosis ,Biopsy ,Cardiomyopathy ,Contrast Media ,Sensitivity and Specificity ,Endomyocardial biopsy ,Young Adult ,Internal medicine ,Image Interpretation, Computer-Assisted ,Humans ,Medicine ,cardiovascular diseases ,Medical diagnosis ,Aged ,Aged, 80 and over ,Heart Failure ,business.industry ,Myocardium ,Hypertrophic cardiomyopathy ,Dilated cardiomyopathy ,Gold standard (test) ,Cardiomyopathy, Hypertrophic ,Middle Aged ,Image Enhancement ,musculoskeletal system ,medicine.disease ,Magnetic Resonance Imaging ,Hypertensive heart disease ,Echocardiography ,Heart failure ,cardiovascular system ,Cardiology ,Female ,Cardiomyopathies ,Cardiology and Cardiovascular Medicine ,business ,Software ,Endocardium ,circulatory and respiratory physiology - Abstract
Aims The diagnostic performance of cardiac magnetic resonance (CMR) has not been compared with that of other imaging modalities. Therefore, this study investigated the diagnostic capabilities of CMR and endomyocardial biopsy (EMB) in patients with heart failure (HF). Methods and results We studied 136 patients with cardiomyopathy who underwent both CMR and EMB. Independent diagnoses were made according to the results of (i) CMR alone; (ii) EMB alone; (iii) clinical data plus echocardiogram; (iv) clinical data, echocardiogram, plus CMR; and (v) clinical data, echocardiogram, plus EMB. These diagnoses were then compared with the final diagnosis (gold standard) that was made using the complete clinical data, including EMB and CMR. The sensitivities of the diagnosis strategies of (i–v) relative to the final diagnosis were 67, 79, 86, 97, and 100%, respectively. CMR alone demonstrated better sensitivity for cardiac sarcoidosis and greater specificity for dilated cardiomyopathy than EMB alone. CMR also tended to show better sensitivity for hypertensive heart disease. There was no difference between the diagnostic capability of CMR and EMB for hypertrophic cardiomyopathy (HCM). However, CMR showed excellent sensitivity (100%) for apical and obstructive HCM, whereas EMB displayed better sensitivity for dilated HCM. Moreover, combined diagnosis with clinical data, echocardiogram, plus CMR achieved superior agreement with the final diagnosis in comparison with EMB alone. Conclusion Non-invasive CMR demonstrated excellent diagnostic capability for patients with HF and was as effective as or superior to EMB. In particular, the use of CMR in combination with clinical data unrelated to EMB may provide excellent diagnostic accuracy for HF.
- Published
- 2013
145. Liposomal Amiodarone Augments Anti-arrhythmic Effects and Reduces Hemodynamic Adverse Effects in an Ischemia/Reperfusion Rat Model
- Author
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Hirokazu Shigematsu, Masaki Yamato, Hiroyuki Takahama, Shoji Sanada, Yoshihiro Asano, Masafumi Kitakaze, Naoto Oku, Hai Ying Fu, Issei Komuro, Tetsuo Minamino, Tomohiro Asai, Hiroshi Asanuma, Keiji Okuda, Masanori Asakura, and Takashi Matsuzaki
- Subjects
Male ,Drug ,medicine.medical_specialty ,media_common.quotation_subject ,Rat model ,Ischemia ,Amiodarone ,Hemodynamics ,Myocardial Reperfusion Injury ,Internal medicine ,medicine ,Animals ,Anti arrhythmic ,Pharmacology (medical) ,Rats, Wistar ,Adverse effect ,media_common ,Pharmacology ,Liposome ,business.industry ,Arrhythmias, Cardiac ,General Medicine ,medicine.disease ,Rats ,Disease Models, Animal ,Liposomes ,Cardiology ,Nanoparticles ,Cardiology and Cardiovascular Medicine ,business ,Anti-Arrhythmia Agents ,medicine.drug - Abstract
Although amiodarone is recognized as the most effective anti-arrhythmic drug available, it has negative hemodynamic effects. Nano-sized liposomes can accumulate in and selectively deliver drugs to ischemic/reperfused (I/R) myocardium, which may augment drug effects and reduce side effects. We investigated the effects of liposomal amiodarone on lethal arrhythmias and hemodynamic parameters in an ischemia/reperfusion rat model.We prepared liposomal amiodarone (mean diameter: 113 ± 8 nm) by a thin-film method. The left coronary artery of experimental rats was occluded for 5 min followed by reperfusion. Ex vivo fluorescent imaging revealed that intravenously administered fluorescent-labeled nano-sized beads accumulated in the I/R myocardium. Amiodarone was measurable in samples from the I/R myocardium when liposomal amiodarone, but not amiodarone, was administered. Although the intravenous administration of amiodarone (3 mg/kg) or liposomal amiodarone (3 mg/kg) reduced heart rate and systolic blood pressure compared with saline, the decrease in heart rate or systolic blood pressure caused by liposomal amiodarone was smaller compared with a corresponding dose of free amiodarone. The intravenous administration of liposomal amiodarone (3 mg/kg), but not free amiodarone (3 mg/kg), 5 min before ischemia showed a significantly reduced duration of lethal arrhythmias (18 ± 9 s) and mortality (0 %) during the reperfusion period compared with saline (195 ± 42 s, 71 %, respectively).Targeting the delivery of liposomal amiodarone to ischemic/reperfused myocardium reduces the mortality due to lethal arrhythmia and the negative hemodynamic changes caused by amiodarone. Nano-size liposomes may be a promising drug delivery system for targeting I/R myocardium with cardioprotective agents.
- Published
- 2013
146. Derivation of a mathematical expression for predicting the time to cardiac events in patients with heart failure: a retrospective clinical study
- Author
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Akira Ishii, Masanori Asakura, Takashi Washio, Takuya Hasegawa, Seiji Takashima, Tetsuo Minamino, Masafumi Kitakaze, Akemi Yoshida, Hiroshi Asanuma, and Hideaki Kanzaki
- Subjects
Male ,medicine.medical_specialty ,Physiology ,Patient Readmission ,Retrospective data ,Japan ,Internal medicine ,Internal Medicine ,Humans ,Medicine ,In patient ,Derivation ,Aged ,Retrospective Studies ,Statistical hypothesis testing ,Aged, 80 and over ,Heart Failure ,business.industry ,Models, Cardiovascular ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Outcome (probability) ,Clinical trial ,Heart failure ,Cardiology ,Female ,Medical emergency ,Cardiology and Cardiovascular Medicine ,business ,Algorithms - Abstract
The prognoses for patients with certain diseases are estimated by averaging the results of clinical trials. To investigate the possibility of deriving a mathematical formula for the estimation of prognosis, we formulated the equation τ=f(x1, …, xp), where x1, …, xp are clinical features and τ represents the clinical outcome for heart failure (HF). We attempted to determine the function to mathematically formulate the relationship between clinical features and outcomes for these patients. We followed 151 patients (mean age: 68.6±14.6 years; men: 61.6%) who were consecutively hospitalized and discharged as a result of acute decompensated HF (ADHF) between May 2006 and December 2009. The mathematical analysis was performed through a probabilistic modeling of the relational data by assuming a Poisson process for rehospitalization owing to HF and by linearly approximating the relationship between the clinical factors and the mean elapsed time to rehospitalization. The former assumption was validated by a statistical test of the data, and the contribution of each parameter was assessed based on the coefficients of the linear relation. Using a regularization method to analyze 402 clinical parameters, we identified 252 factors that substantially influenced the elapsed time until rehospitalization. With the probability model based on the Poisson process, the actual (X; 388±377 days) and estimated (Y; 398±381 days) elapsed times to rehospitalization were tightly correlated (Y=1.0076X+6.5531, R(2)=0.9879, P
- Published
- 2012
147. A simple construction of regulator indecomposable higher Chow cycles in elliptic surfaces
- Author
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Masanori Asakura, Matt Kerr, and Gregory Pearlstein
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Pure mathematics ,Simple (abstract algebra) ,Regulator ,Calculus ,Indecomposable module ,Mathematics - Published
- 2016
148. Prognostic Impacts of Metabolic Syndrome in Patients With Chronic Heart Failure - A Multicenter Prospective Cohort Study
- Author
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Yasuhiko Sakata, Toshiro Miura, Soichiro Tadaki, Satoshi Yasuda, Kazunori Shimada, Takeshi Yamamoto, Yoshihiro Fukumoto, Hiroaki Shimokawa, Yutaka Miura, Masafumi Yano, Masafumi Kitakaze, Toshiaki Kadokami, Satoshi Miyata, Shin-ichi Ando, Hiroyuki Daida, and Masanori Asakura
- Subjects
Male ,medicine.medical_specialty ,Waist ,Population ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Prevalence ,Humans ,030212 general & internal medicine ,Obesity ,Prospective Studies ,education ,Prospective cohort study ,Aged ,Heart Failure ,Metabolic Syndrome ,education.field_of_study ,business.industry ,Incidence (epidemiology) ,Hazard ratio ,General Medicine ,medicine.disease ,Heart failure ,Chronic Disease ,Cardiology ,Female ,Metabolic syndrome ,Cardiology and Cardiovascular Medicine ,business ,Dyslipidemia - Abstract
BACKGROUND Metabolic syndrome (MetS) is involved in the increased risk of atherosclerotic cardiovascular diseases. We have previously reported that the prevalence of MetS is more than 2-fold greater in patients with chronic heart failure (CHF) than in the general population in Japan. However, the prognostic impact of MetS in CHF patients remains to be elucidated. METHODS AND RESULTS In the present nationwide, large-scale clinical study in Japan, we enrolled 4,762 patients with Stage C/D CHF. The prevalence of MetS by the definition of the Japanese Committee for the Diagnostic Criteria in 2005 was 41.3% (50.6% in males, 21.5% in females). MetS was characterized by higher prevalence of males, obesity and lifestyle-related comorbidities, including glucose intolerance, dyslipidemia and hypertension. Multivariate Cox hazard analysis showed that MetS was associated with increased incidence of the composite of all-cause death and atherosclerotic events in males (hazard ratio [HR] 1.28; 95% confidence interval [CI] 1.06-1.54, P=0.011) but not in females (HR 1.23, 95% CI 0.87-1.75, P=0.241). Among the components of MetS, over waist circumference and glucose intolerance were significantly associated with increased incidence of the composite endpoint (HR 1.23, P=0.038, and HR 1.29, P
- Published
- 2016
149. Syntomic cohomology and Beilinson’s Tate conjecture for 𝐾₂
- Author
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Masanori Asakura and Kanetomo Sato
- Subjects
Pure mathematics ,Algebra and Number Theory ,Geometry and Topology ,Cohomology ,Mathematics ,Tate conjecture - Abstract
We study Beilinson’s Tate conjecture for K 2 K_2 using the theory of syntomic cohomology. As an application, we construct integral indecomposable elements of K 1 K_1 of elliptic surfaces. Moreover, we give the first example of a surface X X with p g ≠ 0 p_g\ne 0 over a p p -adic field such that the torsion of C H 0 ( X ) \mathrm {CH}_0(X) is finite.
- Published
- 2012
150. Quintic surface over 𝑝-adic local fields with infinite 𝑝-primary torsion in the Chow group of 0-cycles
- Author
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Masanori Asakura
- Published
- 2012
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