10 results on '"R. Toh"'
Search Results
2. Fish-Derived Omega-3 Fatty Acids: Guardians of High-Density Lipoprotein?
- Author
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Toh R
- Subjects
- Animals, Fish Oils, Lipoproteins, HDL, Fatty Acids, Omega-3
- Published
- 2023
- Full Text
- View/download PDF
3. A Novel Indicator for HDL Functionality.
- Author
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Irino Y, Toh R, and Ishida T
- Subjects
- Animals, Coronary Artery Disease etiology, Coronary Artery Disease metabolism, Humans, Lipoproteins, HDL blood, Biomarkers analysis, Coronary Artery Disease prevention & control, Dyslipidemias complications, Lipoproteins, HDL physiology
- Published
- 2019
- Full Text
- View/download PDF
4. Assessment of HDL Cholesterol Removal Capacity: Toward Clinical Application.
- Author
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Toh R
- Subjects
- Animals, Cardiovascular Diseases blood, Cholesterol, HDL blood, Humans, Prognosis, Risk Assessment, Cardiovascular Diseases etiology, Cholesterol, HDL deficiency
- Abstract
While there is a controversy regarding the causal relationship between high-density lipoprotein cholesterol (HDL-C) and cardiovascular disease (CVD), recent studies have demonstrated that the cholesterol efflux capacity (CEC) of HDL is associated with the incidence of CVD. However, there are several limitations to current assays of CEC. First, CEC measurements are not instantly applicable in clinical settings, because CEC assay methods require radiolabeled cholesterol and cultured cells, and these procedures are time consuming. Second, techniques to measure CEC are not standardized. Third, the condition of endogenous cholesterol donors would not be accounted for in the CEC assays. Recently, we established a simple, high-throughput, cell-free assay system to evaluate the capacity of HDL to accept additional cholesterol, which is herein referred to as "cholesterol uptake capacity (CUC)". We demonstrated that CUC represents a residual cardiovascular risk in patients with optimal low-density lipoprotein cholesterol control independently of traditional risk factors, including HDL-C. Establishing reproducible approaches for the cholesterol removal capacity of HDL is required to validate the impact of dysfunctional HDL on cardiovascular risk stratification in the "real world".
- Published
- 2019
- Full Text
- View/download PDF
5. Cardioprotective Effects of High-Density Lipoprotein Beyond its Anti-Atherogenic Action.
- Author
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Nagao M, Nakajima H, Toh R, Hirata KI, and Ishida T
- Subjects
- Animals, Humans, Atherosclerosis metabolism, Atherosclerosis prevention & control, Cardiotonic Agents therapeutic use, Cholesterol, HDL metabolism
- Abstract
High-density lipoprotein cholesterol (HDL-C) has been identified as a powerful independent negative predictor of cardiovascular disease. The beneficial effect of HDL is largely attributable to its key role in reverse cholesterol transport, whereby excess cholesterol in the peripheral tissues is transported to the liver, reducing the atherosclerotic burden. However, mounting evidence indicates that HDL also has pleiotropic properties, such as anti-inflammatory, anti-oxidative, and vasodilatory properties, which may contribute in reducing the incidence of heart failure. Actually, previous data from clinical and experimental studies have suggested that HDL exerts cardioprotective effects irrespective of the presence/absence of coronary artery disease. This review summarizes the currently available evidence regarding beneficial effects of HDL on the heart beyond its anti-atherogenic property. Understanding the mechanisms of cardiac protection by HDL will provide new insight into the underlying mechanism and therapeutic strategy for heart failure.
- Published
- 2018
- Full Text
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6. Association between Serum Elaidic Acid Concentration and Insulin Resistance in Two Japanese Cohorts with Different Lifestyles.
- Author
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Itcho K, Yoshii Y, Ohno H, Oki K, Shinohara M, Irino Y, Toh R, Ishida T, Hirata KI, and Yoneda M
- Subjects
- Blood Glucose, Cohort Studies, Cross-Sectional Studies, Female, Follow-Up Studies, Glucose Intolerance blood, Glucose Tolerance Test, Humans, Insulin blood, Japan epidemiology, Male, Middle Aged, Oleic Acids, Prognosis, Biomarkers blood, Glucose Intolerance epidemiology, Insulin Resistance, Life Style, Oleic Acid blood
- Abstract
Aim: Many cohort studies have shown that increased trans fatty acid (TFA) intake increases the risk of developing coronary heart disease. However, whether TFA intake is directly associated with the development of diabetes mellitus (DM) remains unknown., Methods: We performed the 75-g oral glucose tolerance test in two Japanese cohorts: a cohort of 454 native Japanese living in Hiroshima, Japan, and a cohort of 426 Japanese-Americans living in Los Angeles, USA, who shared identical genetic predispositions but had different lifestyles. Serum elaidic acid concentration was measured and compared, and its association with insulin resistance was assessed., Results: Serum elaidic acid concentrations were significantly higher in the Japanese-Americans (median, 18.2 µmol/L) than in the native Japanese (median, 11.0 µmol/L). The serum elaidic acid concentrations in the native Japanese DM group (16.0 µmol/L) were significantly higher compared with those in the normal glucose tolerance (10.8 µmol/L) and impaired glucose tolerance (11.7 µmol/L) groups. Multiple linear regression analyses showed that serum elaidic acid concentrations were significantly positively associated with homeostasis model assessment for insulin resistance (HOMA-IR) values after adjusting for various factors., Conclusions: These results suggest that excessive TFA intake worsens insulin resistance and increases the risk of developing DM even in the native Japanese, whose intakes of animal fat and simple carbohydrates were presumed to be lower than those of the Japanese-Americans.
- Published
- 2017
- Full Text
- View/download PDF
7. Enhanced Impact of Cholesterol Absorption Marker on New Atherosclerotic Lesion Progression After Coronary Intervention During Statin Therapy.
- Author
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Mori K, Ishida T, Tsuda S, Oshita T, Shinohara M, Hara T, Irino Y, Toh R, and Hirata KI
- Subjects
- Aged, Biomarkers metabolism, Case-Control Studies, Coronary Angiography, Coronary Artery Disease etiology, Coronary Artery Disease metabolism, Female, Follow-Up Studies, Humans, Male, Middle Aged, Prognosis, Risk Factors, Anticholesteremic Agents adverse effects, Apolipoprotein B-48 metabolism, Cholesterol metabolism, Coronary Artery Disease pathology, Intestinal Absorption drug effects, Percutaneous Coronary Intervention adverse effects
- Abstract
Aim: Clinical trials suggest that residual risks remain for coronary artery disease (CAD) during low-density lipoprotein cholesterol (LDL-C) lowering therapy. We aimed to investigate the role of exogenous lipids in the prognosis of CAD after percutaneous coronary intervention (PCI)., Methods: A total of 145 patients with CAD, who underwent elective PCI, and 82 non-CAD (control) patients were enrolled in this study. CAD patients underwent follow-up coronary angiography 6-9 months after PCI, and were classified into three groups: 1) patients who showed in-stent restenosis (ISR) in the original stented segment, 2) patients with other non-target coronary atherosclerotic lesions (de novo), and 3) patients with neither ISR nor a de novo lesion. Biochemical analyses were performed on fasting serum samples at the time of follow-up coronary angiography., Results: Despite the controlled serum LDL-C levels, CAD patients with statin showed elevated cholesterol absorption marker campesterol/total cholesterol (TC), synthesis marker lathosterol/TC, campesterol/lathosterol ratio, and apolipoprotein B48 (apoB48) concentration compared with non-CAD patients. The high campesterol/TC, campesterol/lathosterol ratio, and apoB48 concentration were associated with de novo lesion progression after PCI. In stepwise multivariate logistic regression analysis, campesterol/TC and apoB48 concentrations were independent risk factors for de novo lesion progression in statin-treated CAD patients after PCI., Conclusion: The increase of cholesterol absorption marker and apoB48 concentration may lead to the progression of de novo lesions, and these markers may represent a residual risk during statin treatment after PCI., Competing Interests: COI Tatsuro Ishida has received lecture honoraria from MSD, and Mochida Pharmaceutical. Ken-ichi Hirata has received resarch funds from Acterion Pharmaceuticals Japan, Sysmex, GlaxoSmithKline, Dai-ichi Sankyo, Japan Medtronics, St. Jude Medical Japan, Sumitomo Dainippon Pharma, Takeda Pharmaceutical, Nippon Boehringer Ingelheim, Boston Scientific Japan, Bristol-Myers Squibb, Mochida Pharmaceutical, FUJI-FILM RI Pharma, Nihon Medi-Physics, Bayer Yakuhin, Astellas Pharma, Eizai, MSD, Kaneka Medix, Novartis Pharma, and Otsuka Pharmaceutical, and lecture honoraria from MSD, AstraZeneca, Takeda Pharmaceutical, Pfizer, Dai-ichi Sankyo, Mochida Pharmaceutical, Kowa Pharmaceutical, and Japanese Society of Internal Medicine. The other authors report no conflicts of interest.
- Published
- 2017
- Full Text
- View/download PDF
8. Plasma activity of endothelial lipase impacts high-density lipoprotein metabolism and coronary risk factors in humans.
- Author
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Sun L, Ishida T, Miyashita K, Kinoshita N, Mori K, Yasuda T, Toh R, Nakajima K, Imamura S, and Hirata K
- Subjects
- Adult, Aged, Aged, 80 and over, Animals, COS Cells, Chlorocebus aethiops, Coronary Artery Disease metabolism, Female, Fluorescent Dyes chemistry, Humans, Immunoglobulin G blood, Immunoprecipitation, Male, Middle Aged, Myocardium enzymology, Phospholipases metabolism, Phospholipids metabolism, Recombinant Proteins metabolism, Risk Factors, Young Adult, Lipase blood, Lipoproteins, HDL blood
- Abstract
Aim: Endothelial lipase (EL) is a determinant of plasma levels of high-density lipoprotein cholesterol (HDL-C). However, little is known about the impact of EL activity on plasma lipid profile. We aimed to establish a new method to evaluate EL-specific phospholipase activity in humans., Methods: Plasma samples were obtained from 115 patients with coronary artery disease (CAD) and 154 patients without CAD. Plasma EL protein was immunoprecipitated using an anti-EL monoclonal antibody after plasma non-specific immunoglobulins were removed by incubation with ProteinA. The phospholipase activity of the immunoprecipitated samples was measured using a fluorogenic phospholipase substrate, Bis-BODIPY FL C11-PC., Results: The EL-specific phospholipase assay revealed that plasma EL activity was inversely correlated with HDL-C levels (R = -0.3088, p<0.0001). In addition, the EL activity was associated with cigarette smoking. Furthermore, EL activity in CAD patients was significantly higher than that in nonCAD patients. Concomitantly, the HDL-C level in CAD patients were significantly lower than that in non-CAD patients., Conclusion: We have established a method for human plasma EL-specific phospholipase activity by combination of EL immunoprecipitation and a fluorogenic phospholipid substrate. Plasma EL activity was associated with not only plasma HDL-C levels but also the risks for CAD.
- Published
- 2014
- Full Text
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9. Pitavastatin increases HDL particles functionally preserved with cholesterol efflux capacity and antioxidative actions in dyslipidemic patients.
- Author
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Miyamoto-Sasaki M, Yasuda T, Monguchi T, Nakajima H, Mori K, Toh R, Ishida T, and Hirata K
- Subjects
- 1-Alkyl-2-acetylglycerophosphocholine Esterase metabolism, Adult, Aged, Antioxidants metabolism, Aryldialkylphosphatase metabolism, Atherosclerosis prevention & control, Cholesterol metabolism, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology, Male, Middle Aged, Platelet Activating Factor metabolism, Polyethylene Glycols metabolism, Cholesterol, HDL drug effects, Dyslipidemias drug therapy, Dyslipidemias metabolism, Quinolines pharmacology
- Abstract
Aim: Although statins increase the plasma concentration of high-density lipoprotein cholesterol (HDL-C), it has not been elucidated whether the increased HDL particles possess normal antiatherosclerotic properties. Pitavastatin functions to increase the plasma HDL-C level and decrease the lowdensity lipoprotein cholesterol (LDL-C) level. In the present study, we sought to examine the qualitative changes in HDL during pitavastatin treatment., Methods: A total of 30 patients with dyslipidemia were treated with 2 mg of pitavastatin for four weeks. The cholesterol efflux capacity and activities of the antioxidative enzymes paraoxonase-1 (PON-1) and platelet-activating factor acetylhydrolase (PAF-AH) were evaluated using polyethethylene glycol-treated HDL fractions before and after pitavastatin treatment., Results: Pitavastatin treatment decreased the serum LDL-C level by 39% and increased the serum HDL-C level by 9% (p<0.05). In addition, pitavastatin increased the phospholipid content of HDL by 7.8% (p<0.05). The pitavastatin-induced increase in the HDL-C level coincided with an increase in the cholesterol efflux capacity of the isolated HDL fraction of 8.6% (p<0.05). The post-pitavastatin treatment activity of HDL-associated PON-1 (paraoxonase and arylesterase) was increased by 9% (p<0.05) and 11% (p<0.05), respectively, while the HDL-associated PAF-AH activity was not affected by pitavastatin., Conclusions: In addition to its LDL-C-lowering effects, pitavastatin elevates the HDL-C level and enhances the cholesterol efflux capacity and antioxidative properties of HDL. Pitavastatin therefore increases the amount of functional HDL without attenuating HDL quality.
- Published
- 2013
- Full Text
- View/download PDF
10. Expression of endothelial lipase correlates with the size of neointima in a murine model of vascular remodeling.
- Author
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Sun L, Ishida T, Okada T, Yasuda T, Hara T, Toh R, Shinohara M, Yamashita T, Rikitake Y, and Hirata K
- Subjects
- Angiotensin II metabolism, Animals, Carotid Artery, Common pathology, Cell Adhesion, Cell Movement, Cell Proliferation, Disease Models, Animal, Dose-Response Relationship, Drug, Extracellular Signal-Regulated MAP Kinases metabolism, Humans, Inflammation, Lipoproteins metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Myocytes, Smooth Muscle cytology, Oxidative Stress, Endothelium, Vascular enzymology, Gene Expression Regulation, Enzymologic, Lipase biosynthesis, Neointima pathology
- Abstract
Aim: Endothelial lipase (EL) regulates plasma high-density lipoprotein-cholesterol (HDL-C) levels by promoting HDL catabolism. However, it remains unknown whether the inhibition of EL has beneficial effects on the genesis of vascular diseases. Here, we investigated the role of EL on vascular remodeling in mice., Methods: Vascular remodeling was developed by ligation of the left common carotid artery and neointimal lesions were histologically compared between EL-knockout (ELKO), EL-transgenic (ELTg), and wild-type (WT) mice. HDL was isolated from these mice, and effects of the HDL on cell growth and Erk activation were evaluated in vitro using cultured vascular smooth muscle cells., Results: Plasma HDL-C levels were 62% higher in ELKO and 13% lower in ELTg than in WT mice, after the carotid ligation. The size of neointimal lesion was significantly larger in ELTg and smaller in ELKO than in WT mice. Vascular expression of adhesion molecules was lower in ELKO and higher in ELTg compared with WT mice. Moreover, oxidative stress was attenuated in ELKO mice. HDL isolated from ELKO, ELTg, and WT mice inhibited expression of intercellular adhesion molecule-1, angiotensin II-induced activation of Erk, and growth of cultured vascular smooth muscle cells, whereas EL expression itself did not affect cell migration or growth., Conclusion: EL expression modulates vascular remodeling as well as plasma HDL-C levels. EL inactivation may increase HDL particles that can inhibit smooth muscle cell growth and migration.
- Published
- 2012
- Full Text
- View/download PDF
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