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Clinical Introduction A 69-year-old woman with hypertension and dyslipidemia developed sudden onset of substernal chest pain at night and was admitted to our hospital the following day. A 12-lead and 18-lead ECG (Nihon Kohden, Japan) was done (figure 1A,B). Question Which is the most likely diagnosis? Reperfused anterior acute myocardial infarction Takotsubo (stressed) cardiomyopathy Pericarditis Apical hypertrophic cardiomyopathy For answer see page 2.

Background Atrial fibrillation (AF), which contributes to an increased risk of stroke, frequently remains undetected, suggesting an unmet need for easier and more reliable AF screening. The reports on screening AF using an Omron blood pressure (BP) monitor with an irregular heartbeat (IHB) detector show inconsistent results, so the aim of this study was to develop a novel algorithm to accurately diagnose AF with 3 BP measurements using an Omron automated BP monitor with IHB detector.Methods and Results:In total, 303 general cardiac patients were included. Real-time single-lead ECG revealed AF in 44 patients. BP measurement was performed 3 times per patient using the Omron BP monitor HEM-907, and the number of IHBs detected was recorded. Based on these data, we developed the following algorithm: ≥1 IHB is detected during at least 2 of 3 BP measurements and the maximum number of IHBs detected is ≥2. Using this algorithm, we achieved a sensitivity of 95.5% and specificity of 96.5%, for diagnosing AF. Conclusions The novel algorithm with 3 BP measurements using the Omron automated BP monitor with IHB detector showed high sensitivity and specificity for diagnosing AF in general cardiac patients.

Aims Sensory information from the lower urinary tract (LUT) is conveyed to the spinal cord to trigger and co-ordinate micturition. However, it is not fully understood how spinal dorsal horn neurons are excited during the voiding reflex. In this study, we developed an in vivo technique allowing recording of superficial dorsal horn (SDH) neurons concurrent with intravesical pressure (IVP) during the micturition cycle in both normal and diabetic rats. Methods Lumbosacral dorsal horn neuronal activity and IVP were recorded from urethane-anesthetized naive and streptozotocin (STZ)-induced diabetic rats. Saline was continuously perfused into the urinary bladder through a cannula to induce micturition. Results We classified SDH neurons into bladder- and urethral-responsive neurons, based on their responsiveness during the voiding reflex. Bladder-responsive SDH neurons responded to the rapid increase in IVP at the start of voiding. In contrast, urethral-responsive SDH neuronal firing increased at the peak IVP and their firing lasted during the voiding phase (the high-frequency oscillations). Urethral-responsive SDH neurons were more sensitive to capsaicin, received C afferent fiber inputs, and were rarely detected in STZ-diabetes rats. Administration of a cyclohexenoic long-chain fatty alcohol (TAC-302), which is reported to promote neurite outgrowth of peripheral nerves in STZ-diabetic rats, prevented the functional loss of spinal urethral response. Conclusions Sensory information from the bladder and urethra is conveyed separately to different groups of SDH neurons. Functional loss of spinal urethral sensory information through unmyelinated C afferent fibers may contribute to diabetic bladder dysfunction.

Twelve-lead electrocardiography provides us the clue about the differential diagnosis between atrioventricular nodal reentrant tachycardia and atrioventricular reentrant tachycardia.

We often observe patients with antiphospholipid syndrome (APS) presenting with both venous and arterial thrombi. Anticoagulant therapy is effective for venous and peripheral arterial embolisms in these patients; however, it has opposite effects when applied for thoracic aortic mural thrombosis because of the risk of new arterial embolisms. Recently, thoracic endovascular aortic repair (TEVAR) has been used to prevent arterial embolisms due to aortic thrombosis. However, we generally hesitate to implant artificial materials in patients in a hypercoagulable state because this can cause new thrombi to develop. Here, we present a case of successful treatment by anticoagulant therapy and TEVAR in an APS patient presenting with pulmonary embolisms (PEs) and multiple arterial embolisms due to thoracic aortic mural thrombosis. A 46-year-old man was referred to our hospital due to dyspnea and leg pain. Since contrast-enhanced computed tomography revealed PEs, thoracic aortic mural thrombosis, and lower limb arterial embolisms, we administered anticoagulation therapy. Three days later, contrast-enhanced computed tomography revealed new arterial embolisms in the right kidney. To prevent further arterial embolisms due to thoracic aortic mural thrombosis, we performed emergent TEVAR in addition to anticoagulant therapy. Thereafter, no venous or arterial embolisms recurred during the 13-month follow-up period.

Background In patients with aneurysmal subarachnoid hemorrhage (SAH), an association between hypocapnia and poor clinical outcomes has been reported. However, the optimal arterial carbon dioxide tension (PaCO2) remains unknown. The present retrospective study aimed to examine the association of abnormal PaCO2 levels with neurological outcomes and investigate the optimal target PaCO2 level in patients with SAH. Methods We retrospectively selected consecutive adult patients hospitalized in the intensive care unit (ICU) for SAH between January 2009 and April 2017. Univariate and multivariate analyses were performed to identify the independent predictors of unfavorable neurological outcomes (i.e., modified Rankin scale score of 3–6 on hospital discharge). Results Among 158 patients with SAH, 73 had unfavorable neurological outcomes. During the first 2 weeks in the ICU, the median number of PaCO2 measurements per patient was 43. The factors significantly associated with unfavorable neurological outcomes were age, Hunt and Kosnik grade, maximum lactate levels during the first 24 h, and maximum (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.03–1.21; p

Objective Home care is important in patients with heart failure (HF) in order to maintain their quality of life. A biomarker that can be measured noninvasively is needed to optimize the home care of patients with HF. Urinary angiotensinogen (uAGT) is an indicator of the intrarenal renin-angiotensin system activity, which may be augmented in HF. We hypothesized that uAGT might be a urinary biomarker in HF. Methods We measured uAGT by an enzyme-linked immunosorbent assay and uAGT normalized by urinary creatinine (uCr)-designated uAGT/uCr-at admission and discharge in 45 patients hospitalized for HF. Results We found that both uAGT/uCr [median (interquartile range): 65.5 (17.1-127.7) μg/g Cr at admission; 12.1 (6.0-37.0) μg/g Cr at discharge; p

Background Atrial fibrillation (AF) is a frequent arrhythmia in pacemaker patients and is associated with poor quality of life and increased risks of heart failure, dementia, stroke, and death. The MINERVA trial has shown that the combination of 3 pacing algorithms – 1) atrial antitachycardia pacing (aATP), 2) atrial preventive pacing and 3) managed ventricular pacing (MVP) - delays progression to persistent and permanent AF, compared with standard DDDR pacing mode and with MVP mode, in pacemaker patients with AF history. Purpose We performed a comparative non randomized evaluation to confirm the hypothesis that aATP is the main driver of persistent/permanent AF reduction independently on the effect of preventive atrial pacing. Methods Thirty-one Italian and Japanese Cardiology centers included consecutive dual-chamber pacemaker patients with AF history. aATP was programmed in all patients while preventive atrial pacing was not enabled. Comparison was made with all the 3 groups in MINERVA randomized trial. The main endpoint was incidence of AF longer than 7 consecutive days, as detected by device diagnostics. Results A total of 146 patients (73 years old, 54% male) were included and followed for a median observation period of 31 months. The 2-year incidence of AF>7 days was 12% in the aATP group, very similar to that found in the arm of the MINERVA trial with aATP enabled (13.8%, p=0.732) and significantly lower than AF incidence found in the MINERVA Control DDDR arm (25.8%, p=0.012) and in the MINERVA MVP arm (25.9%, p=0.025). Conclusions In a real-world population of dual-chamber pacemaker patients with AF history, use of aATP was associated with low incidence of persistent AF during follow up, highlighting that the positive results of the MINERVA trial are related to the effectiveness of aATP rather than to the effects of preventive atrial pacing. Funding Acknowledgement Type of funding source: None

Objective The MINERVA trial showed that in pacemaker patients with atrial fibrillation (AF) history, DDDRP pacing combining three algorithms - (a) atrial antitachycardia pacing with Reactive ATP enabled, (b) atrial preventive pacing and (c) managed ventricular pacing (MVP)-may effectively delay progression to persistent/permanent AF compared with standard DDDR pacing. We performed a comparative non-randomised evaluation to evaluate if Reactive ATP can be the main driver of persistent/permanent AF reduction independently on preventive pacing. Methods Thirty-one centres included consecutive dual-chamber pacemaker patients with AF history. Reactive ATP was programmed in all patients while preventive atrial pacing was not enabled. These patients were compared with the three groups of MINERVA randomised trial (Control DDDR, MVP, and DDDRP). The main endpoint was the incidence of AF longer than 7 consecutive days. Results A total of 146 patients (73 years old, 54% male) were included and followed for a median observation period of 31 months. The 2-year incidence of AF > 7 days was 12% in the Reactive ATP group, very similar to that found in the DDDRP arm of the MINERVA trial (13.8%, P = .732) and significantly lower than AF incidence found in the MINERVA Control DDDR arm (25.8%, P = .012) and in the MINERVA MVP arm (25.9%, P = .025). Conclusions In a real-world population of dual-chamber pacemaker patients with AF history, the use of Reactive ATP is associated with a low incidence of persistent AF, highlighting that the positive results of the MINERVA trial were related to the effectiveness of Reactive ATP rather than to preventive pacing.

AIMS To evaluate the therapeutic effect of TAC-302, a cyclohexenoic fatty alcohol derivative, on bladder denervation-related storage and voiding dysfunctions in rats with bladder outlet obstruction (BOO). METHODS BOO was achieved by partial ligature of the proximal urethra in female rats. Two weeks later, BOO rats were divided into two groups and treated orally with vehicle or 10 mg/kg TAC-302 twice a day for 4 weeks. Urodynamic and immunohistochemical evaluation of the bladder muscle layer was performed. In another study, the BOO rats were treated with intravenous tamsulosin at cystometry. The detrusor contractility in each group was evaluated using the modified Shafer's nomogram. RESULTS Two weeks after BOO, the rats showed significant increases in non-voiding contraction (NVCs) and residual urine volume (RUV) compared to the sham group. Moreover, 6 weeks after BOO, BOO vehicle rats showed significant increases in NVCs and RUV and decreases in detrusor contractility and in the nerve fiber density in the urinary bladder compared to the sham group. BOO-induced denervation of the urinary bladder was partially improved by oral treatment with TAC-302. Oral treatment with TAC-302 significantly reduced the amplitude and frequency of NVCs (P

Deterioration of adipocyte function due to increased oxidative stress predisposes patients to metabolic disorders in advanced age. However, the roles of tumor suppressors in such conditions remain largely unknown. Therefore, we aimed to address their dynamics in aged adipocytes using a long-term culture model. We compared 3T3-L1 adipocytes at 17–19 days (long-term) with those at 8–10 days (short-term) after initiation of adipogenic induction for mimicking ‘aged’ and ‘young’ adipocytes, respectively. H2O2 release and dihydroethidium (DHE) staining was increased, while superoxide dismutase (SOD) activity was reduced in long-term cultured adipocytes, which is suggestive of enhanced oxidative stress in this group. Moreover, qRT-PCR revealed increased mRNAs of Nox4 (a subunit of NADPH oxidase complex), Ccl2 (a proinflammatory chemokine) and Il6 [a marker of senescence-associated secretory phenotype (SASP)] along with decreased levels of Pparγ, Adipoq and Slc2a4 (genes related to glucose metabolism). These alterations were associated with increased expression of the tumor suppressors alternate-reading-frame protein p19Arf (Arf) and p16Ink4a. However, silencing of Arf reduced mRNAs of Adipoq and Slc2a4 and enhanced release of Il6. The effect was opposite in Arf overexpressing adipocytes, which showed reduced superoxide production as assessed with DHE staining and SOD activity. Western blots showed that Arf negatively regulates the phosphorylation of Akt. Luciferase assay in Hela cells additionally suggested that Arf negatively regulates Il6 transcriptional activity through a PI3 K/Akt mediated pathway. These findings strongly suggest that the enhanced Arf expression in oxidative stress plays compensatory protective roles against aging-related dysregulation of gene expression in adipocytes.

Adult aortic coarctation is often asymptomatic and this condition can be detected because of a murmur or unexplained hypertension. Here, we report an adult case of aortic coarctaion with heart failure and a characteristic finding of pulsation below the bilateral clavicle. A 58-year-old man with refractory heart failure due to unknown reasons was referred to our hospital. Auscultation presented no murmur and high blood pressure had been treated with medicine. Interestingly, precise physical examination revealed the bilateral pulsation at the midclavicular line from the 2nd to the 5th intercostal areas. Echographic examination revealed the dilated vessel and arterial blood flow 1–2 cm in depth from the body surface at the midclavicular 2nd intercostal areas. Contrast-enhanced computed tomography showed thoracic aortic coarctation and a well-developed collateral circulation via the bilateral internal thoracic arteries and epigastric arteries. The cause of heart failure was diagnosed as aortic coarctation. Palliative revascularization was performed and his blood pressure was lowered. When we see the patients with refractory heart failure due to unknown reasons, pulsation below the bilateral clavicle may give us a clue to diagnose the “hidden” aortic coarctation.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates expression of low-density lipoprotein (LDL) receptors via receptor internalization and subsequent lysosomal degradation. Thus, an anti-PCSK9 antibody is well known as an anti-hyperlipidemia drug. Here, we aimed to develop vaccine for a long-term treatment of dyslipidemia targeted to PCSK9. In This study, we designed a peptide vaccine for mouse PCSK-9, which consisted of short peptides conjugated to keyhole limpet hemocyanin (KLH) as a carrier protein. Vaccines were administered to male apolipoprotein E (ApoE) deficient mice with adjuvants and significantly elicited an antibody response against PCSK9. The PCSK9 vaccines were administered to mice three times in 2-week intervals, and antibody titers and lipoprotein levels were evaluated up to 24 weeks after the first immunization to determine the therapeutic effect. Anti-PCSK9 antibody titers reached peak levels 6 weeks after the first immunization, and theses titers were maintained for up to 24 weeks. Decreased plasma levels of total cholesterol, very low-density lipoprotein (VLDL), and chylomicron (CM) were maintained for up to 24 weeks. Immunized mice exhibited a significant increase in cell-surface LDL receptor expression. Stimulation with KLH, but not PCSK9, induced the production of INF-gamma and interleukin-4 (IL-4), as determined with ELISPOT assays, thus indicating that PCSK9 vaccine did not elicit T-cell activation in our vaccine system. The present anti-PCSK9 vaccine induced long-lasting anti-PCSK9 antibody production and improved lipoprotein profiles. Thus, anti-PCSK9 vaccine could become a new option for the treatment of dyslipidemia as a long-acting therapy in future.

Background The impact of nicorandil as adjunctive therapy for percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI) is controversial. We performed 15O-labeled water positron emission tomography (PET) to quantify regional myocardial perfusion in patients with STEMI who received nicorandil or no adjunctive therapy during PCI. Methods PCI was performed within 8 h after STEMI onset in 33 patients. 14 patients received intracoronary nicorandil 2 mg immediately after recanalization of the culprit lesion (Nico group). After 3–4 weeks, PET was performed in which myocardial blood flow (MBF) was measured at baseline and during adenosine triphosphate (ATP)-induced hyperemia. Myocardial vascular resistance (MVR) was calculated for all segments. Data were obtained from the reperfused (Rep) and normal segments (Cont) in each patient. Results In patients not given nicorandil (No-Nico group), the MBF was significantly lower in Rep than that in Cont at baseline and during hyperemia (Cont vs. Rep: 0.82 ± 0.14 vs. 0.68 ± 0.11, P = 0.001, ATP-Cont vs. ATP-Rep: 2.00 ± 0.72 vs. 1.52 ± 0.61, P = 0.017), which was restored in the Nico group (Cont vs. Rep: 0.79 ± 0.17 vs. 0.78 ± 0.20; ATP-Cont vs. ATP-Rep: 2.02 ± 0.84 vs. 1.84 ± 0.62). MVR was elevated in Rep at baseline and during hyperemia in the No-Nico group. MVR elevation in Rep was prevented in the Nico group. Conclusions 15O-labeled water PET was feasible for segmental analysis of MBF during the subacute phase of STEMI. It revealed that intracoronary administration of nicorandil to STEMI patients who underwent PCI prevented MVR elevation and thus restored MBF in the reperfused segments to a level similar to that in the normal segments., Highlights • 15O-labeled water positron emission tomography (PET) is a tool to compare directly reperfused segments with normal segments simultaneously in each patient's hearts. • 15O-labeled water PET permits noninvasive quantitative measurement of myocardial blood flow during the subacute phase of myocardial infarction. • 15O-labeled water PET detects restoration of myocardial blood flow after intracoronary administration of nicorandil in STEMI patients.

Vascular endothelial growth factor-A (VEGF-A) released from adipocytes promotes angiogenesis; and thereby ameliorates the local hypoxia-induced adipose inflammation and insulin resistance. Here, we newly found that eicosapentaenoic acid (EPA) upregulated both mRNA expression and release of VEGF-A in mature 3T3-L1 adipocytes. Silencing mRNA of G-protein coupled receptor 120 (GPR120) and specific inhibition of peroxisome proliferator-activated receptor γ (PPARγ) by GW9662 respectively attenuated the EPA-induced augmentation of VEGF-A release by adipocytes. Furthermore, transfection of GPR120 gene alone and PPARγ gene alone to HEK293 cells respectively increased the promoter activity of VEGF-A as assessed by luciferase reporter assay, which was further augmented when both genes were co-transfected. Promoter deletion analysis and chromatin immunoprecipitation assay revealed that co-transfection of GPR120 enhanced EPA-induced PPARγ binding to PPAR-response element in VEGF-A promoter region. Thus, by the synchronized activation of a membrane receptor GRP120 and a nuclear receptor PPARγ, EPA enhances VEGF-A production in adipocytes.

Background 18F-FDG PET has been used in sarcoidosis for diagnosis and determination of the extent of the disease. However, assessing inflammatory lesions in cardiac sarcoidosis using 18F-FDG can be challenging because it accumulates physiologically in normal myocardium. Another radiotracer, 3′-deoxy-3′-18F-fluorothymidine (18F-FLT), has been investigated as a promising PET tracer for evaluating tumor proliferative activity. In contrast to 18F-FDG, 18F-FLT uptake in the normal myocardium is low. The purpose of this retrospective study was to compare the uptake of 18F-FLT and 18F-FDG in the evaluation of cardiac and extra-cardiac thoracic involvement in patients with newly diagnosed sarcoidosis. Data for 20 patients with newly diagnosed sarcoidosis were examined. 18F-FLT and 18F-FDG PET/CT studies had been performed at 1 h after each radiotracer injection. The patients had fasted for at least 18 h before 18F-FDG PET/CT but were given no special dietary instructions regarding the period before 18F-FLT PET/CT. Uptake of 18F-FLT and 18F-FDG was examined visually and semiquantitatively using maximal standardized uptake value (SUVmax). Results Two patients had cardiac sarcoidosis, 7 had extra-cardiac thoracic sarcoidosis, and 11 had both cardiac and extra-cardiac thoracic sarcoidosis. On visual analysis for diagnosis of cardiac sarcoidosis, 4/20 18F-FDG scans were rated as inconclusive because the 18F-FDG pattern was diffuse, whereas no FLT scans were rated as inconclusive. The sensitivity of 18F-FDG PET/CT for detection of cardiac sarcoidosis was 85%; specificity, 100%; and accuracy, 90%. The corresponding values for 18F-FLT PET/CT were 92, 100, and 95%, respectively. Using semiquantitative analysis of cardiac sarcoidosis, the mean 18F-FDG SUVmax was significantly higher than the mean 18F-FLT SUVmax (P

We present a case of myocarditis with increased

Background 18F-FDG PET has been used in sarcoidosis for diagnosis and determination of the extent of the disease. However, assessing inflammatory lesions in cardiac sarcoidosis using 18F-FDG can be challenging because it accumulates physiologically in normal myocardium. Another radiotracer, 3′-deoxy-3′-18F-fluorothymidine (18F-FLT), has been investigated as a promising PET tracer for evaluating tumor proliferative activity. In contrast to 18F-FDG, 18F-FLT uptake in the normal myocardium is low. The purpose of this retrospective study was to compare the uptake of 18F-FLT and 18F-FDG in the evaluation of cardiac and extra-cardiac thoracic involvement in patients with newly diagnosed sarcoidosis. Data for 20 patients with newly diagnosed sarcoidosis were examined. 18F-FLT and 18F-FDG PET/CT studies had been performed at 1 h after each radiotracer injection. The patients had fasted for at least 18 h before 18F-FDG PET/CT but were given no special dietary instructions regarding the period before 18F-FLT PET/CT. Uptake of 18F-FLT and 18F-FDG was examined visually and semiquantitatively using maximal standardized uptake value (SUVmax). Results Two patients had cardiac sarcoidosis, 7 had extra-cardiac thoracic sarcoidosis, and 11 had both cardiac and extra-cardiac thoracic sarcoidosis. On visual analysis for diagnosis of cardiac sarcoidosis, 4/20 18F-FDG scans were rated as inconclusive because the 18F-FDG pattern was diffuse, whereas no FLT scans were rated as inconclusive. The sensitivity of 18F-FDG PET/CT for detection of cardiac sarcoidosis was 85%; specificity, 100%; and accuracy, 90%. The corresponding values for 18F-FLT PET/CT were 92, 100, and 95%, respectively. Using semiquantitative analysis of cardiac sarcoidosis, the mean 18F-FDG SUVmax was significantly higher than the mean 18F-FLT SUVmax (P

BACKGROUND The lipid component of coronary plaques is associated with their vulnerability. The aim of this study was to investigate which coronary risk factors were relevant in predicting serial changes in the lipid component of coronary plaques as evaluated by integrated backscatter intravascular ultrasound (IB-IVUS).Methods and Results:We enrolled 104 patients who underwent IB-IVUS-guided percutaneous coronary intervention (PCI) and were followed up with repeat IB-IVUS 6 months later. We investigated the serial changes in the plasma lipoprotein levels and the percentage of the lipid component of coronary plaques on IB-IVUS. In the multivariate linear regression analysis, the low-density lipoprotein-cholesterol/high-density lipoprotein-cholesterol (L/H) ratio independently had a significant fixed effect with the percentage of the lipid component of coronary plaques at the time of PCI. In addition, the change in the L/H ratio at the 6-month follow-up was significantly associated with that in the lipid component of coronary plaques (regression coefficient, 9.645; 95% CI: 5.814-13.475; P

How nutritional excess leads to inflammatory responses in metabolic syndrome is not well characterized. Here, we evaluated the effects of ω-3 polyunsaturated fatty acid specific G-protein coupled receptor 120 (GPR120) activation on inflammatory pathways in adipocytes, and the influence of this process on macrophage migration. Using 3T3-L1 adipocytes, we found that agonizing GPR120 using its synthetic ligand, GSK137647, attenuated both basal and lipopolysaccharide-induced production of interleukin-6 (IL-6) and C-C motif chemokine ligand 2 (CCL2). Moreover, the intervention reduced the phosphorylation of nuclear factor kappa B inhibitor alpha (IκBα) and nuclear translocation of nuclear factor kappa-B p65 subunit (p65). Furthermore, the silencing of GPR120 itself reduced IL-6 and CCL2 mRNA expression. Inhibition of protein kinase C (PKC) augmented the down-regulatory effect of GSK137647 on IL-6 and CCL2 mRNA. Using a luciferase assay to measure promoter activity of the IL-6 gene in mouse embryonic fibroblasts, we demonstrated that exogenous transfection of GPR120 alone reduced the promoter activity, which was augmented by GSK137647. Inhibition of PKC further reduced the promoter activity. Nevertheless, RAW 264.7 macrophages grown in conditioned medium collected from GSK137647-treated adipocytes attenuated the expressions of matrix metalloproteinases-9 and -3, and tissue inhibitor of metalloproteinase-1. Conditioned medium also inhibited the lipopolysaccharide-induced migration of these macrophages. Taken together, these findings provide critical evidence that although GPR120 is associated with a PKC-mediated pro-inflammatory pathway, the direct inhibitory effects of GPR120 on the nuclear factor kappa B pathway are anti-inflammatory. Moreover, GPR120 activity can attenuate the adipocyte-mediated enhanced production of extracellular matrix-modulating factors in macrophages and can reduce their migration by a paracrine mechanism.

Vascular and cardiac valve calcification is associated with cardiovascular mortality in the general population. Increasing clinical and experimental evidence suggests that inflammation accelerates the progression of calcification, which has molecules in common with bone metabolism. For example, osteopontin (OPN), osteoprotegerin (OPG), receptor activator of the nuclear factor κB ligand (RANKL), and alkaline phosphatase (ALP) are proposed to play central roles in the calcification or demineralization of atherosclerotic lesions and the calcification of cardiac valves. Abnormalities in the balance of these proteins may lead to perturbations in vascular/valve calcification. "How to prevent calcification" is a common task based on conventional data; however, several pathological findings indicate that heavily calcified plaques are stable, which may not lead to coronary events. Vulnerable plaques tend to be either noncalcified or only mildly or moderately calcified. "How to treat calcification," which depends on the details of the specific patient, thus remains a difficult challenge. In addition to the detection of calcification, characterization as well as quantification of it is necessary for optimal treatment of this pathology in the future.

We present a case of myocarditis with increased 18F-FDG uptake and no 18F-fluorothymidine (FLT) uptake.

Highlights: {yields} Mechanisms for preadipocyte hyperplasia by pioglitazone, a PPAR{gamma} agonist, are shown. {yields} Pioglitazone promotes cell-cycle of 3T3-L1 preadipocytes and increases their number. {yields} Pioglitazone downregulates a cyclin dependent kinase inhibitor, p16{sup Ink4a}. {yields} PPAR{gamma} transrepresses p16{sup Ink4a} gene in preadipocytes, which pioglitazone enhances. -- Abstract: Pioglitazone, a synthetic ligand of peroxisome proliferator-activated receptor (PPAR){gamma}, causes preadipocyte proliferation through a mechanism which still remains elusive. Here, to address the mechanism, we investigated the effects of PPAR{gamma} and pioglitazone on the kinetics of cyclin-dependent kinase inhibitors, especially with p16{sup Ink4a} (p16) centered, by employing 3T3-L1 preadipocytes. Pioglitazone promoted preadipocyte proliferation by increasing S and G{sub 2}/M cell-cycle entry, which was accompanied by decreased p16 mRNA expression. PPAR{gamma} overexpression along with the luciferase reporter assay confirmed that PPAR{gamma} was crucial for the downregulation of p16 mRNA transcription, and that the action was augmented by pioglitazone. Thus, pioglitazone exerted cell-cycle dependent promoting effect on preadipocyte proliferation, of which mechanisms include p16-downregulation through PPAR{gamma}.

Left ventricular (LV) hypertrophy (LVH) may be eccentric or concentric (2 × LV posterior wall thickness relative to LV end-diastolic dimension ≤ 0.42 or > 0.42, respectively). The LV diastolic function between age-matched hypertensive patients with eccentric and concentric LVH was compared in the present study. Echocardiography was used to measure LV mass index (LV mass/body surface area; LVMI) as an index of LVH. LV diastolic function was assessed by measurements of peak early transmitral flow velocity ( E)/peak late transmitral flow velocity ( A) (the E/A ratio), peak early diastolic mitral annular velocity ( e′) and the E/e′ ratio. Although LVMI, E/A and e′ did not differ between the two groups, E/e′ was significantly higher (worse) in patients with concentric LVH (13.4 ± 5.4) than in those with eccentric LVH (11.1 ± 3.6). Among hypertensive patients with LVH, those with concentric LVH may, therefore, have more severe LV diastolic dysfunction than those with eccentric LVH even if their LVMIs, which reflect the degree of LVH, are similar.

Although visit-to-visit variability in systolic blood pressure (SBP) has recently been demonstrated to be a strong predictor of stroke, there are no data about relationships between SBP variability and cardiac damage in hypertensive patients. We compared relationships between visit-to-visit variability in SBP and left ventricular (LV) diastolic dysfunction with the relationships between the mean SBP value and cardiac parameters in treated patients. Forty treated hypertensive patients (69 ± 9 years of age) had their blood pressure measured at outpatient clinics every 1 or 2 months over a 1-year period. The standard deviation (s.d.) of SBP and the difference between the maximum and minimum SBPs during this year were calculated to assess visit-to-visit variability. The mean SBP during the year was also calculated. LV diastolic function was assessed by the ratio (E/A) of early (E) and late (A) diastolic transmitral flows, early diastolic mitral annular velocity (e') and the ratio (E/e') of E to e' using Doppler echocardiography. E/A only correlated with the s.d. of SBP (r=-0.327, P=0.040), whereas e' correlated with s.d. of SBP (r=-0.496, P=0.001) and maximum-minimum SBP difference (r=-0.490, P=0.001). E/e' correlated with s.d. of SBP (r=0.384, P=0.014), maximum-minimum SBP difference (r=0.410, P=0.009), and the mean value of SBP (r=0.349, P=0.028). Multiple regression analysis demonstrated only the maximum-minimum SBP difference independently associated with E/e' (β=0.410, P=0.009). Thus, the visit-to-visit variability of SBP showed better correlation with LV diastolic dysfunction than mean values of SBP. High visit-to-visit variability of SBP was associated with LV diastolic dysfunction and may constitute a high risk for diastolic heart failure in hypertensive patients.

We examined which echocardiographic parameter correlated best with plasma brain natriuteric peptide (BNP) levels in treated hypertensive patients. Enrolled in the study were 122 treated hypertensive patients (70 ± 9 y). The left ventricular mass index and left atrial dimension (LAD) were measured using echocardiography as indexes of left ventricular hypertrophy and left atrial enlargement, respectively. Among all the echocardiographic parameters, LAD correlated best with BNP (r = 0.343, p < 0.001). Stepwise regression analysis showed that LAD (β coefficient = 0.513, p < 0.001) was independently associated with BNP. Left atrial enlargement, rather than left ventricular hypertrophy, may be clinically useful for predicting elevated BNP levels in treated hypertensive patients.

Recent studies demonstrated a possible role of aldosterone in mediating cell senescence. Thus, the aim of this study was to investigate whether aldosterone induces cell senescence in the kidney and whether aldosterone-induced renal senescence affects the development of renal injury. Aldosterone infusion (0.75 μg/h) into rats for 5 weeks caused hypertension and increased urinary excretion rates of proteins and N-acetyl-β-D-glucosaminidase. Aldosterone induced senescence-like changes in the kidney, exhibited by increased expression of the senescence-associated β-galactosidase, overexpression of p53 and cyclin-dependent kinase inhibitor (p21), and decreased expression of SIRT1. These changes were abolished by eplerenone (100 mg/kg/d), a mineralocorticoid receptor (MR) antagonist, but unaffected by hydralazine (80 mg/liter in drinking water). Furthermore, aldosterone induced similar changes in senescence-associated β-galactosidase, p21, and SIRT1 expression in cultured human proximal tubular cells, which were normalized by an antioxidant, N-acetyl L-cysteine, or gene silencing of MR. Aldosterone significantly delayed wound healing and reduced the number of proliferating human proximal tubular cells, while gene silencing of p21 diminished the effects, suggesting impaired recovery from tubular damage. These findings indicate that aldosterone induces renal senescence in proximal tubular cells via the MR and p21-dependent pathway, which may be involved in aldosterone-induced renal injury.