Long noncoding Mirt2 reduces apoptosis to alleviate myocardial infarction through regulation of the miR-764/PDK1 axis.

Acute myocardial infarction (AMI) is a common clinical cardiovascular disease, which is the leading cause of death and disability worldwide. Abnormal expression of long noncoding RNAs (lncRNA) is reported to be related to myocardial dysfunctions such as myocardial infarction (MI). In this study, we aimed to investigate the role of lncRNA myocardial infarction-related transcription factors 2 (Mirt2) in AMI and the underlying molecular mechanisms in vivo and in vitro. In vivo AMI model was established by occlusion of the left anterior descending coronary artery. Rats were randomly divided into two groups (five rats per group): the sham group and the AMI group. H9c2 cells were cultured under hypoxia for 4 h and then cultured under normoxia to establish the in vitro hypoxia reoxygenation (H/R) model. Our study shows that the myocardial infarct size and the apoptosis in AMI rats were both significantly increased, indicating that the AMI rat model was successfully established. Additionally, the levels of Mirt2 in AMI rats were increased significantly. Knockdown of Mirt2 by shRNA (shMirt2) had no significant effect on apoptosis and MI in sham rats, but significantly promoted apoptosis and MI in AMI rats. In vitro experiments showed that shMirt2 significantly decreased the level of Mirt2 in H9c2 cells and H9c2 cells treated with H/R. It is worth noting that shMirt2 had no significant effect on H9c2 cells, but significantly increased the levels of oxidative stress markers (malondialdehyde and lactate dehydrogenase), and also increased the number of apoptosis of H/R-treated H9c2 cells. Further mechanistic analysis showed that Mirt2 could protect MI and apoptosis in AMI rats by competitively adsorbing miR-764 and reducing the inhibitory effect of miR-764 on 3-phosphoinositide-dependent kinase 1 (PDK1). More importantly, after overexpression of Mirt2, MI and apoptosis were significantly improved in AMI rats, indicating that Mirt2 showed a protective effect in AMI rats. In summary, these findings suggest that that Mirt2 participated in the regulation of MI through the miR-764/PDK1 axis. Therefore, the current findings provide a theoretical basis for the diagnosis and treatment of clinical MI with changes in Mirt2 levels.

Repetitive Transient Ischemia-Induced Cardiac Angiogenesis is Mediated by Camkii Activation.

BACKGROUND/AIMS: Coronary angiogenesis is an important protective mechanism in response to myocardial ischemia in coronary artery disease. However, the underlying mechanisms remain largely unclear. Here, we investigated the role of CaMKII activation in ischemia-induced cardiac angiogenesis. METHODS: Repetitive transient ischemia model was established in C57/BL6 mice by daily multiple episodes (3 times/day) of short time (5 min) occlusion of the left anterior descending coronary artery for 7 days. Coronary angiogenesis was detected by immunofluorescent staining. RT-qPCR and Western blot analyses were used to detect the mRNA and protein levels of CaMKII, p-CaMKII and VEGF. Primary cardiac microvascular endothelial cells (CMECs) were isolated to investigate the effects of KN93 on cell proliferation and migration in hypoxic condition. RESULTS: We found that angiogenesis was induced in the ischemic myocardium and suppressed by chronic intraperitoneal injection of CaMKII inhibitor KN93. RT-qPCR and Western blot analyses showed that myocardial ischemia induced an increased expression and autophosphorylation of CaMKII. VEGF expression was increased in the ischemia model but blunted by KN93. Moreover, KN93 suppressed the proliferation and migration of cardiac endothelial cells in hypoxic condition in which the protein expression of CaMKII, p-CaMKII and VEGF was increased. CONCLUSION: CaMKII is an important mediator for the ischemia-induced coronary angiogenesis, in which CaMKII-triggered VEGF expression plays a key role.

Endovascular vs. medical therapy in symptomatic vertebral artery stenosis: a meta-analysis.

This meta-analysis aims to compare percutaneous transluminal angioplasty (PTA) to medical treatment (MT) for symptomatic vertebral artery stenosis (SVAS) treatment. We searched PubMed, Springer, Google Scholar, Clinical Trials, Cochrane Central, Chinese National Knowledge Infrastructure, and China Biological Medicine databases. All relevant comparative trials were included. All summary estimates were calculated by random-effect models. Ten comparative trials involving 672 patients were identified. Within 30-day follow-up, there was no significant difference between PTA plus MT and MT alone in vascular death, any stroke, posterior circulation TIA, posterior circulation infarction, and ischemic stroke (all P > 0.05). With a follow-up of more than 1 year, no significant difference was found between PTA plus MT and MT alone in all-cause death (3 vs. 7 %, P = 0.24), vascular death (4 vs. 7 %, P = 0.34), posterior circulation stroke (5 vs. 8 %, P = 0.48), posterior circulation ischemic events (8 vs. 25 %, P = 0.23), posterior circulation TIA (10 vs. 38 %, P = 0.11), posterior circulation infarction (6 vs. 12 %, P = 0.51), vertebral artery occlusion (6 vs. 12 %, P = 0.58), and in secondary long-term events, including any stroke, anterior circulation stroke, hemorrhagic stroke, and myocardial infarction (all P > 0.05), although PTA plus MT could largely reduce the vertebral artery stenosis rate [MD 63.05 %, 95 % CI (32.77-93.34 %), P < 0.01]. Hence, PTA plus MT may be not superior to MT alone for SVAS treatment. Larger randomized trials are needed to verify the optimum therapy for SVAS.

The Efficacy and Safety of Tolvaptan in Patients with Hyponatremia: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND OBJECTIVES: Comprehensive evaluations regarding the benefits of tolvaptan in the treatment of hyponatremia are lacking. The objective of this meta-analysis was to assess the efficacy and safety of tolvaptan in patients with hyponatremia. METHODS: Pertinent studies were identified by searching PubMed, EMBASE, Web of Science, and the Cochrane Library for articles published between their respective inception dates and 31 April 2016. Summary relative risks (RRs) or weighted mean differences (WMDs) with their 95 % confidence intervals (CIs) were calculated using fixed-effects or randomized-effects models, depending on the degree of heterogeneity noted among the studies included in the analysis. RESULTS: Eleven articles comprising 5209 patients were ultimately included in the analysis. Our pooled results showed that tolvaptan was more effective than control with respect to increasing serum sodium concentrations (WMD = 3.99 mEq/L), 95 % CI 2.80-5.19, Z = 6.56, P < 0.001), improving serum sodium correction rates (RR = 3.35, 95 % CI 1.93-5.82, Z = 4.31, P < 0.001), improving 24-h urine output (WMD = 987.64 mL, 95 % CI 850.71-1124.57, Z = 14.14, P < 0.001), and improving net fluid balance (WMD = 795.97 mL, 95 % CI 418.56-1173.38, Z = 4.13, P < 0.001). Tolvaptan treatment also resulted in increased incidences of adverse events compared with control treatment (RR = 1.05, 95 % CI 1.02-1.07, Z = 3.83, P < 0.001). These events included dry mouth (RR = 2.38, 95 % CI 1.41-4.04, Z = 3.23, P = 0.001), thirst (RR = 3.85, 95 % CI 1.96-7.57, Z = 3.92, P < 0.001), pollakiuria (RR = 2.47, 95 % CI 1.41-4.33, Z = 3.16, P = 0.002), and overly rapid hyponatremia correction (RR = 8.43, 95 % CI 1.06-66.96, Z = 2.02, P = 0.04). No significant differences in all-cause mortality (RR = 0.99, 95 % CI 0.90-1.10, Z = 0.17, P = 0.86), serious adverse event rate (RR = 1.01, 95 % CI 0.80-1.29, Z = 0.11, P = 0.92), systolic blood pressure (WMD = 0.1 mmHg, 95 % CI -1.04 to 1.23, Z = 0.17, P = 0.87), or heart rate (WMD = -0.16 bpm, 95 % CI -1.14 to 0.82, Z = 0.31, P = 0.76) were noted between the two groups, based on the results of our meta-analysis. CONCLUSION: The results of this meta-analysis suggest that tolvaptan can increase serum sodium concentrations, serum sodium correction rates, 24-h urine output, net fluid balance, and total adverse event rates without significantly decreasing all-cause mortality rates or increasing serious adverse event rates in patients with hyponatremia.

Meta-analysis comparing the effects of rosuvastatin versus atorvastatin on regression of coronary atherosclerotic plaques.

Rosuvastatin and atorvastatin both are high-intensity statins. However, which statin is more effective for the reversion of coronary atherosclerotic plaques remains inconclusive. We, therefore, conducted a meta-analysis to provide further evidence for proper statin selection. Pubmed, The Cochrane Library, Embase, Chinese BioMedicine, and China National Knowledge Infrastructure databases were systematically searched for eligible publications. We also manually reviewed the references from all relevant literature for more trials. Only studies that met our predefined inclusion criteria up to March 31, 2015, were enrolled. Five randomized controlled trials, 4 published in English and 1 in Chinese, were finally included in our study with a total of 1,556 participants, of whom 772 were in the rosuvastatin group and 784 in the atorvastatin group. The dose ratios of rosuvastatin versus atorvastatin were 1:2 in all included trials. Pooling across the studies demonstrated that compared with atorvastatin, rosuvastatin administration further reduced the total atheroma volume (weighted mean difference [WMD] -1.61 mm(3), 95% confidence interval [CI] -2.70 to -0.52; p = 0.004) and percent atheroma volume (WMD -0.34%, 95% CI -0.64 to -0.03; p = 0.03) and improved the lumen volume more significantly (WMD 2.10 mm(3), 95% CI 0.04 to 4.17; p = 0.046). The comparative regression of plaques was not different across subgroups. In conclusion, rosuvastatin is superior to atorvastatin in the reversion of coronary atherosclerotic plaques.