miR-1268a Regulates Fatty Acid Metabolism by Targeting CD36 in Angiotensin II-induced Heart Failure.

Multiple RNAs have been involved in the progress of heart failure. However, the role of miR-1268a in heart failure is still unclear. The differentially expressed miRNAs in heart failure was analyzed based on GEO dataset GSE104150. AC16 cells were treated with Angiotensin II (Ang II) to explore the role of miR-1268a in heart failure. The web tool miRWalk was used to analyze the targets of miR-1268a. miR-1268a was up-regulated in Ang II-treated AC16 cells. Ang II treatment markedly inhibited cell proliferation, ATP production, fatty acid (FA) uptake and enhanced levels of HF markers BNP and ST2, and oxidative stress of AC16 cells. Notably, inhibition of miR-1268a eliminated the inhibiting effect of Ang II on cell proliferation, ATP production, FA uptake and decreased levels of BNP an ST2, and oxidative stress on AC16 cells. Furthermore, CD36 was a target of miR-1268a and the CD36 level was decreased by miR-1268a mimics but increased by miR-1268a inhibitor in AC16 cells. miR-1268a regulates FA metabolism and oxidative stress in myocardial cells by targeting CD36 in heart failure.

Predictive value of quality of life as measured by KCCQ in heart failure patients: A meta-analysis.

BACKGROUND: Studies on the predictive ability of disease-specific health quality of life (QoL) in patients with heart failure (HF) have produced conflicting results. To address these gaps in knowledge, we conducted a meta-analysis to evaluate the predictive value of QoL measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) in patients with HF. MATERIALS AND METHODS: We searched PubMed, and Embase databases to identify studies investigating the predictive utility of baseline QoL measured by the KCCQ in HF patients. The outcome measures were all-cause mortality and HF hospitalisation. The predictive value of QoL was expressed by pooling the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the bottom versus the top category of KCCQ score or for per 10-point KCCQ score decrease. RESULTS: Twelve studies reporting on 11 articles with a total of 34,927 HF patients were identified. Comparison of the bottom with the top KCCQ score, the pooled adjusted HR was 2.34 (95% CI 2.10-2.60) and 2.53 (95% CI 2.23-2.88) for all-cause mortality and HF hospitalisation, respectively. Additionally, a 10-point decrease in KCCQ score was associated with a 12% (95% CI 7%-16%) increased risk of all-cause mortality and a 14% (95% CI 13%-15%) increased risk of HF hospitalisation. CONCLUSIONS: Poor health-related QoL as determined by the lower KCCQ score, was associated with an increased risk of all-cause mortality and HF hospitalisation in patients with HF. Measuring disease-specific health-related QoL using the KCCQ score may provide valuable predictive information for HF patients.

Efficacy and safety of antiplatelet therapy in COVID-19: Insights from a meta-analysis of randomized controlled trials.

BACKGROUND: COVID-19 induces a pro-coagulant state with thrombotic events. This meta-analysis explores the efficacy and safety of antiplatelet-based therapy in COVID-19 patients through randomized controlled trials (RCTs). MATERIALS AND METHODS: A systematic literature search until March 10, 2023, identified 7 RCTs involving 23,415 inpatients. Of these, 11,891 received antiplatelet-based treatment, and 11,524 received placebo/other drugs. Statistical analysis was performed using Review Manager 5.4. RESULTS: The included trials involved patients with a mean age ranging from 54.3 to 62.0 years and a prevalence of hypertension ranging from 10.9 to 65.0% and coronary artery disease ranging from 3.2 to 32.7%. The pooled analysis showed no significant difference in overall mortality between groups (RR 1.0, 95% CI 0.99 - 1.01, p = 0.76). However, antiplatelet therapy significantly reduced major thrombotic events (RR 0.86, 95% CI 0.75 - 0.99, p = 0.04). Conversely, it increased major bleeding risks (RR 1.62, 95% CI 1.24 - 2.12, p = 0.0005). There was no significant difference in the incidence of invasive mechanical ventilation and respiratory death. CONCLUSION: Antiplatelet therapy does not confer mortality benefit in COVID-19 patients but lowers major thrombotic events while increasing major bleeding risks. Ongoing large RCTs will provide more information on the therapeutic value of this therapy.

A meta-analysis of randomized controlled trials of statin-based therapy in patients with COVID-19.

BACKGROUND: Previous observational studies and meta-analyses have suggested that statins could be beneficial in reducing the risk of adverse clinical outcomes. This study is the first to conduct a meta-analysis of recently published randomized controlled clinical trials investigating the potential therapeutic benefits of statins for COVID-19. MATERIALS AND METHODS: A thorough search was conducted using databases such as PubMed and Embase until May 2023 to identify randomized controlled clinical trials investigating the use of statins in patients with COVID-19. Review Manager 5.4 was used to analyze the selected studies. RESULTS: Seven randomized controlled trials comprising a total of 2,370 patients were included in this study. Of these, 1,295 patients received statin therapy, while 1,075 received placebo or other drugs. All included studies were conducted on inpatients with an average age of 45 - 61 years, and the proportion of patients with diabetes and coronary heart disease was less than 30%. One study only included severely ill patients. Our results showed that statin treatment did not significantly reduce hospitalized patient mortality (11.5 vs. 13.4%, p = 0.94), the proportion of patients transferred to intensive care due to disease changes (14.2 vs. 11.2%, p = 0.41), or the proportion of patients requiring mechanical ventilation (5.3 vs. 7.9%, p = 0.71) compared to controls. However, the use of statins was associated with a slight increase in hospital stay. CONCLUSION: A critical appraisal of published randomized controlled trials on statin therapy in COVID-19 did not show any significant effect on mortality, the risk of transfer to intensive care, or mechanical ventilation.

MicroRNA-126 and VEGF enhance the function of endothelial progenitor cells in acute myocardial infarction.

Previous studies have found that microRNA-126 (miR-126) overexpression can exert beneficial effects on endothelial function and angiogenesis. The role of miR-126 was previously reported to be by directly limiting the activities of negative regulators of the vascular endothelial growth factor (VEGF) pathway, such as PI3K regulation subunit 2 (PIK3R2). The aim of the present study was to investigate the role of the miR-126/PIK3R2/VEGF axis in endothelial progenitor cells (EPCs) under hypoxic conditions. An in vitro hypoxia model in EPCs was established by exposing EPCs to hypoxia (O2/N2/CO2, 1/94/5) for 72 h, before reverse transcription-quantitative PCR (RT-qPCR) and western blot analyzes were used to measure miR-126 and PIK3R2 expression in EPCs. The proliferation, migration and tube-forming ability of the transfected cells were measured using MTT, Transwell and tube formation assays, respectively. miR-126 expression was found to be lower in EPCs in the hypoxia group compared with that in the control group (P<0.01). The expression of PIK3R2, a direct target gene of miR-126, was found to be higher in the hypoxia group compared with that in the control group (P<0.01). miR-126 mimic and VEGF-plasmid co-transfection improved the proliferation, migration, tube-forming ability and restored the phosphorylation of AKT in EPCs under hypoxic conditions (all P<0.01). In addition, the effects of miR-126 mimic on hypoxia-induced EPCs were reversed by PIK3R2-plasmid co-transfection, whilst the effects of VEGF-plasmid were enhanced further by co-transfection with the miR-126 mimic. In conclusion, miR-126 promoted the functions of EPCs under hypoxic conditions by negatively targeting PIK3R2, whilst the combined overexpression of miR-126 and VEGF enhanced these aforementioned effects.

Hypoxia-inducible transcription factor-1α inhibition by topotecan protects against lipopolysaccharide-induced inflammation and apoptosis of cardiomyocytes.

BACKGROUND: Myocarditis, an inflammatory disease of the myocardium, is a serious hazard to human life due to the expansion of inflammatory lesions in the myocardium. The aim of this study was to investigate the role of hypoxia-inducible transcription factor (HIF)-1α and its inhibitor topotecan in the pathogenesis of myocarditis. METHODS: H9c2 cardiomyoblasts was stimulated with lipopolysaccharide (LPS) to simulate myocarditis model in vitro. The levels of myocardial damage markers were determined using commercially available kits. Western blotting was used to evaluate HIF-1α expression after LPS challenge. Then, after HIF-1α silencing, the contents of inflammatory factors were determined with enzyme-linked immunosorbent assay (ELISA). Cell viability was tested by means of a cell counting kit-8 (CCK-8) assay. Cell apoptosis was assessed by flow cytometry, and the expression of apoptotic proteins was examined using western blot analysis. Subsequently, HIF-1α was overexpressed and topotecan was employed to treat H9c2 cells under LPS exposure condition. The biological functions were detected again. RESULTS: LPS significantly elevated the levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB) and cardiac troponin-I (cTn-I) in supernatant of H9c2 cell lysates. Additionally, LPS led to the notably upregulated expression of HIF-1α. HIF-1α-knockdown markedly decreased the concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8 compared with the LPS-induced group. Moreover, the cell viability was conspicuously enhanced and cell apoptotic ratio was remarkably reduced, accompanied by downregulated expression of Bax, Bim, caspase 3 and caspase 9 after HIF-1α silencing. Consistently, HIF-1α gain-of-function significantly promoted the production of inflammatory cytokines and cell apoptosis, which was partially counteracted by topotecan administration. CONCLUSION: To conclude, these findings demonstrated that HIF-1α inhibition by topotecan ameliorates LPS-induced myocarditis in vitro, providing a new approach in the treatment of myocarditis.

Traditional Chinese medicine Qili qiangxin inhibits cardiomyocyte apoptosis in rats following myocardial infarction.

The aim of the present study was to examine the effect of the traditional Chinese medicine Qili qiangxin on cardiomyocyte apoptosis following myocardial infarction (MI) in a rat model. MI was induced in rats by ligation of the anterior descending coronary artery. Survivors were randomly divided into the sham operation, MI, and Qili qiangxin groups (4 g/kg per day). After 28 days, infarction size was measured. In the non-infarcted zones (NIZ), the apoptotic index (AI) was measured by terminal deoxynucleotidyl transferase (TdT)-mediated digoxigenin-conjugated dUTP nick-end labeling (TUNEL). Expression of Fas was detected by immunohistochemistry, and the expression of xanthine oxidase (XO) and caspase-3 by western blot analysis. In addition, the XO and ·O2-, ·OH-scavenging activity of myocardial tissue in NIZ was measured by colorimetry. Compared to the MI group, AI and the expression of Fas and caspase-3 were significantly decreased in NIZ. The activity of XO was also considerably reduced while ·O2- and ·OH-scavenging activity was significantly increased in the Qili qiangxin group. Ventricular remodeling was attenuated but there were no significant differences in infarct size (IS) or XO expression levels between the Qili qiangxin and MI groups. In conclusion, the results suggest that Qili qiangxin may inhibit cardiomyocyte apoptosis in NIZ in rats. The potential mechanism involved may be associated with its ability to reduce reactive oxygen species (ROS) and to depress the expression of Fas and caspase-3.

Angiotensin-(1-7) attenuates angiotensin II-induced signalling associated with activation of a tyrosine phosphatase in Sprague-Dawley rats cardiac fibroblasts.

BACKGROUND INFORMATION: Angiotensin-(1-7) [ANG-(1-7)] mediates vasodilation, antiproliferation, anti-apoptosis and antifibrosis, therefore, it opposes the effects of angiotensin II (ANG II). However, the detailed signal transduction mechanism following the Mas receptor activated by ANG-(1-7) is still poorly understood. Src homology2-containing inositol phosphatase 1 (SHP-1), a redoxsensitive protein tyrosine phosphatase, negatively influences downstream signalling molecules, such as mitogen-activated protein kinases (MAPKs), through dephosphorylation, thereby inhibiting proliferative and profibrotic signalling induced by ANG II. Therefore, we hypothesised that SHP-1 may mediate the antiproliferative signalling of ANG-(1-7) through the regulation of the dynamic balance of MAPKs and SHP-1 in isolated cardiac fibroblasts. Primary culture of neonatal Sprague-Dawley rats cardiac fibroblasts was treated separately with different interventions to investigate this issue. RESULTS: Our data revealed that ANG II increased the phosphorylation of extracellular signal-related kinase (p-ERK1/2) and the ratio of (p-ERK1/2)/(ERK1/2), but ANG-(1-7) decreased them. The effects of ANG-(1-7) on the phosphorylation p-ERK1/2 were blocked by the Mas receptor antagonist A-779. Unlike ANG II, which decreased the activity of SHP-1, ANG-(1-7) increased its activity. Overexpression of SHP-1 attenuated the ANG II-stimulated phosphorylation of c-Src, its downstream molecules ERK1/2, α-smooth muscle actin and transforming growth factor-ß1 (TGF-ß1). These effects were also inhibited by the specific inhibitor of SHP-1, sodium stibogluconate. ANG-(1-7) had no significant effects on the gene expression of TGF-ß1, collagen I or collagen III, but was found to antagonise the stimulatory effects of ANG II on them. CONCLUSIONS: ANG-(1-7), through Mas receptor, activates SHP-1 in cardiac fibroblasts, which can negatively modulate ANG II-induced phosphorylation of c-Src and MAPKs, and inhibits profibrotic factors TGF-ß1 and collagen production. ANG-(1-7) can thereby serve as a protective role by counteracting the effects of ANG II.