Alarin alleviated cardiac fibrosis via attenuating oxidative stress in heart failure rats.

The present study was to explore whether alarin could alleviate heart failure (HF) and attenuate cardia fibrosis via inhibiting oxidative stress. The fibrosis of cardiac fibroblasts (CFs) was induced by angiotensin (Ang) II. HF models were induced by ligation of the left anterior descending artery to cause ischemia myocardial infarction (MI) in Sprague-Dawley rats. Alarin (1.0 nM/kg/d) was administrated by intraperitoneal injection for 28 days. The decreases of left ventricular (LV) ejection fraction (EF), fractional shortening (FS), the maximum of the first differentiation of LV pressure (LV ± dp/dtmax) and LV systolic pressure (LVSP), and the increases of LV volume in systole (LVVS), LV volume in diastole (LVVD), LV end-systolic diameter (LVESD) and LV end-diastolic diameter (LVEDD) in MI rats were improved by alarin treatment. The increases in the expression levels of collagen I, collagen III, and transforming growth factor (TGF)-ß were inhibited by alarin treatment in CFs and in the hearts of MI rats. The levels of NADPH oxidase (Nox) activity, superoxide anions and malondialdehyde (MDA) levels were increased, and the level of superoxide dismutase (SOD) activity was reduced in Ang II-treated CFs, which were reversed by alarin. Nox1 overexpression reversed the effects of alarin on attenuating the increases of collagen I, collagen III and TGF-ß expression levels induced by Ang II in CFs. These results indicated that alarin improved HF and cardiac fibrosis via inhibiting oxidative stress in HF rats. Nox1 played important roles in the regulation of alarin effects on attenuating CFs fibrosis induced by Ang II.

Clinical pharmacodynamics and long-term efficacy of Talcom vs. Plavix in patients undergoing coronary stent implantation: a randomized study with 5-year follow-up.

PURPOSE: Form II clopidogrel bisulfate (Plavix) has been extensively used in patients with acute coronary syndrome. However, the efficacy of form I clopidogrel bisulfate (Talcom) was less investigated. The aim of this study was to investigate the efficacy and safety of Talcom compared with Plavix. METHOD: Two hundred and forty-eight patients were recruited after receiving percutaneous coronary intervention (PCI). Participants were randomly assigned to Talcom or Plavix group, and administered with Talcom or Plavix 75 mg od respectively in combination with aspirin 100 mg od for 12 months. Primary endpoints were set as levels of adenosine diphosphate-induced platelet aggregation (PLADP) on the 5th day and at 1 month after randomization. Patients were followed-up for 5 years. Bleeding events and major adverse cardiovascular events (MACE) including cardiac death, non-fatal myocardial infarction, ischemic stroke, target lesion revascularization (TLR), and cardiogenic re-admission were recorded. RESULTS: On the 5th day and at 1 month after randomization, the antiplatelet effect of Talcom was non-inferior to that of Plavix [PLADP (5th day): 30% (22%, 43%) vs. 33% (22%, 44%), p = 0.007; PLADP (1 month): 29% (19%, 43%) vs. 31% (22%, 43%), p = 0.005]. A total of 208 patients completed the follow-up, the incidences of MACE and bleeding were both comparable, and the MACE-free survival did not differ between the two groups. However, the expenditure was 32% lower for Talcom compared to Plavix during the treatment period. CONCLUSIONS: The antiplatelet effect of Talcom is non-inferior to Plavix, and the clinical efficacy and safety of Talcom and Plavix at 5 years were not significantly different in this study.

Tumstatin (69-88) alleviates heart failure via attenuating oxidative stress in rats with myocardial infarction.

Background: This study aimed to elucidate the effects of tumstatin (69-88) on heart failure and the underlying mechanism. Materials and methods: Myocardial infarction (MI) was induced by ligating the left coronary artery in rats to trigger heart failure. Results: Tumstatin (69-88) can reduce cardiac insufficiency in rats with heart failure. The increased cardiac fibrosis in MI rat was attenuated by tumstatin (69-88). Increase of cardiac atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in rats with myocardial infarction, and Ang II-treated NRCMs or H9C2 cells was inhibited by tumstatin (69-88). In the heart of MI rats, and Ang II-treated NRCMs or H9C2 cells, the superoxide anions and NADPH oxidase (Nox) activity rose and the superoxide dismutase (SOD) activity was reduced, which was inhibited by tumstatin (69-88). Diethyldithiocarbamate, an SOD inhibitor, increased the ANP and BNP in NRCMs or H9C2 cells. Tumstatin (69-88) inhibited the Ang II-induced raises of ANP and BNP in NRCMs or H9C2 cells, which was reversed by DETC. Conclusions: These results indicate that tumstatin (69-88) alleviates cardiac dysfunction of heart failure. Tumstatin (69-88) improves the hypertrophy of cardiomyocytes via attenuation of oxidative stress. Tumstatin (69-88) may be a potential drug for heart failure in the future.

Use of handheld electrocardiograph (SnapECG) for the remote monitoring of arrhythmias.

Objective: To investigate the value of a SnapECG monitoring in diagnosing arrhythmias compared with the conventional management. Methods: In the first phase, the SnapECG and 12-lead electrocardiogram (ECG) were simultaneously adopted to detect arrhythmias in 439 hospitalized patients. The accuracies of the SnapECG in detecting different arrhythmias were assessed. In the second phase, 62 patients with palpitations were randomized to receive the SnapECG monitoring or conventional management for 3 months. The diagnosis rate, time of diagnosis, episodes before diagnosis, associated expenses, and scores of the modified European Heart Rhythm Association (EHRA), Self-rating Anxiety Scale (SAS), and the 36-item short-form health survey questionnaire (SF-36) were compared between groups. Results: In the first phase, the SnapECG monitoring showed a sensitivity of 83.55% and specificity of 96.79% in identifying tachyarrhythmias, and a sensitivity of 95.29% and specificity of 97.54% in identifying bradyarrhythmias. In the second phase, 1642 ECGs were recorded by the SnapECG, among which 290 abnormal ECGs were identified. Compared with the conventional management, the SnapECG monitoring increased the diagnosis rate of symptomatic arrhythmias (70.97% vs. 19.35%, P < 0.05), shortened the time of diagnosis (48.26 ± 36.78 days vs. 71.45 ± 30.01 days, P < 0.05) and consequently reduced the episodes of symptomatic arrhythmias prior to establishing diagnosis. The scores of modified EHRA, SAS, SF-36 significantly improved at 3-month compared with their baseline levels in the SnapECG group. Conclusions: Remote monitoring with the SnapECG can achieve early diagnosis of symptomatic arrhythmias. However, its sensitivity in identifying P-wave-related arrhythmias warrants further improvement.

Hypomethylation of Rnase6 Promoter Enhances Proliferation and Migration of Murine Aortic Vascular Smooth Muscle Cells and Aggravates Atherosclerosis in Mice.

Background: Accumulating evidence has implicated DNA methylation in the progression of atherosclerosis (AS). Rnase6 has been reported to be upregulated in AS development, but the specific regulatory mechanism remains unclear. Material/Methods: Peripheral blood and sclerotic plaque tissues from 25 AS patients were collected to detect Rnase6 expression. Methylation-specific polymerase chain reaction (MSP) was used to detected Rnase6 methylation levels in the peripheral blood of AS patients. Rnase6 expression was knocked down or DNA methyltransferase 1 (DNMT1) was overexpressed in OX-LDL-treated mouse aortic smooth muscle cells (MOVAS), and cell proliferation, migration, ROS content, and inflammatory factor secretion levels were detected. 740 Y-P, a PI3K specific agonist, was introduced to verify the effect of Rnase6 promoter hypomethylation on the PI3K/Akt signaling pathway. We knocked down Rnase6 expression in ApoE-/- mice fed with a high-fat diet to examine Rnase6 promoter methylation levels. Plaque areas and inflammatory factor secretion were examined in AS mice overexpressing DNMT1. Results: Rnase6 expression was upregulated in the peripheral blood and plaque tissues of AS patients, accompanied by decreased methylation levels of the Rnase6 promoter. Interfering with Rnase6 expression or overexpressing DNMT1 in OX-LDL stimulated MOVAS inhibited cell proliferation and migration, decreased ROS content and inflammatory factor secretion, and inhibited PI3K pathway protein expression. Rnase6 expression was decreased in the peripheral blood and plaque tissues of si-Rnase6-injected mice, and Rnase6 promoter methylation was increased. Mice overexpressing DNMT1 showed less plaque areas in the aortic root and lower secretion levels of inflammatory factors. Conclusion: Hypomethylation of the promoter of Rnase6 enhanced the proliferation and migration of OX-LDL treated MOVAS, upregulated ROS content and inflammatory factor secretion levels in the cells, and activated the PI3K/Akt signaling pathway.