Effects of Exercise Therapy on Anxiety and Depression in Patients With Coronary Heart Disease: A Meta-Analysis of a Randomized Controlled Study.

Objective: The purpose of this review was to evaluate the effect of exercise therapy on anxiety and depression symptoms in patients with coronary heart disease (CHD). Methods: A systematic review of papers published between January 2000 and February 2021 was conducted. MEDLINE, Embase, the Cochrane Library and Web of Science were searched. Meta-analysis was used to compare the results of the included studies. Bias risk assessment was performed using the Cochrane Collaboration bias risk tool. If half or more of the seven items in Randomized controlled trials (RCTs) were low-risk, then the RCT was considered low-risk research; otherwise, it was high-risk. Statistical analyses were performed using RevMan version 5.3 and STATA version 12.0. Results: We performed a meta-analysis of 11 randomized clinical studies including 771 subjects. Eight studies (73%) were of high quality. Compared with the control group, the exercise group showed a significant improvement in anxiety [standard mean difference (SMD) = -0.61; 95% confidence interval (CI): -0.86, -0.35]. The depression level in the exercise group was also significantly reduced (SMD = -0.48; 95% CI: -0.92, -0.04). Aerobic fitness and athletic endurance also improved [mean difference (MD) = 0.77; 95% CI: 0.58, 0.95; and MD = 20.69; 95% CI: 6.91, 34.46; respectively]. Conclusions: This meta-analysis suggests that exercise therapy may be effective in alleviating anxiety and depression symptoms in patients with coronary heart disease. Due to methodological weaknesses, rigorous research needs to be designed to further confirm the effectiveness of exercise therapy in improving the mental health of patients with coronary heart disease. Systematic Review Registration: https://inplasy.com/projects/, identifier: INPLASY202160017.

MicroRNA-20a participates in the aerobic exercise-based prevention of coronary artery disease by targeting PTEN.

BACKGROUND: Exercise can reduce the coronary artery disease (CAD) incidence. MiRNA-20a has been reported to distinctly expressed after sustain physical activity. However, its expression and regulation pattern in CAD model with or without exercise has not been reported. OBJECTIVE: In present study, we aim to investigate regulatory mechanism of miR-20a in exercise-associated reduced-CAD incidence and miR-20a-dependent signaling pathways. METHODS: Eight weeks old male ApoE/LDLR double knock out mice were recruited for this study. CAD model was established in mice fed with or without western diet and cholesterol levels were measured using detection kit as well as fast protein liquid chromatography. Relative mRNA levels were determined using quantitative RT-PCR while the protein levels were analyzed using western blotting. Luciferase assay was used to determine the miRNA binding site on target genes. CCK-8 assay and flow cytometry (FCM) were used for assessing the proliferative and apoptotic rate. RESULTS: Overall cholesterol level was significantly increased in CAD model group, compared to normal control group. Expression of miR-20 was significantly lower in CAD group where the VEGF and PTEN were upregulated, compared to non-CAD group. Increased miR-20a was induced after exercise in CAD model group, and miR-20a agomir group. Overexpression of miR-20a decreased the expression level of ET-1, TxA2, ANGII, PTEN and increased the eNOS, PGI2, and VEGF, at both transcriptional and translational levels. In vitro examination further confirmed these findings in human umbilical vein endothelial cells (HUVEC). MiR-20a specifically binds to the 3'UTR of PTEN and mediated the cell survival and proliferation through activating the PI3K/Akt signaling pathways. CONCLUSION: MiRNA-20a may have great potential as therapeutic target for CAD, since its participation can induce alteration of functional genes as well as PTEN, which is specifically targeted by miR-20a, and promote the survival and proliferation of vein endothelial cells.

Design and Development of Novel 4-(4-(1H-Tetrazol-5-yl)-1H-pyrazol-1-yl)-6-morpholino-N-(4-nitrophenyl)-1,3,5-triazin-2-amine as Cardiotonic Agent via Inhibition of PDE3.

The classical phosphodiesterase 3A (PDE3A) inhibitors provide relaxation of the vasculature system via increasing the cellular level of cyclic adenosine monophosphate (cAMP) and proved to be useful in the management of congestive heart failure. Consequently, the present paper deals with the development of novel pyrazole derivatives tethered with substituted 1,3,5-triazine derivatives in search for novel PDE3 inhibitors. The synthesis of designed inhibitors was realized in a multi-step reaction and the structures were ascertained with the help of various spectroscopic techniques. Subsequently, these analogs were tested for their inhibitory activities against PDE3 enzymes, where they exhibited considerable inhibition, revealing 9g as the most promising inhibitor of the class. In a docking study, the morpholine fragment of compound 9g was efficiently engulfed in the small pocket of the active site lined by Gly940 and Pro941. The substituted aromatic ring of the core scaffold was found to be positioned deep in the cavity bordered by Tyr829, Asn830, Leu850, Glu851, and Thr893. Moreover, it considerably improved the contractility of cardiac muscles without altering the heart beat frequency in experimental subjects.

BET protein inhibition mitigates acute myocardial infarction damage in rats via the TLR4/TRAF6/NF-κB pathway.

Acute myocardial infarction (AMI) is among the most serious cardiovascular diseases and is a leading cause of mortality in developed countries. Previous studies have indicated the central role played by the bromodomain (BRD) proteins, which belong to the BRD and extra-terminal (BET) family, in gene control during heart failure pathogenesis. In addition, BET inhibition has been shown to suppress cardiomyocyte hypertrophy. However, the role of BET proteins in myocardial infarction remains unclear. The present study aimed to investigate whether BETs inhibition mitigates AMI, and explore the molecular mechanism underlying this effect. A rat model of acute myocardial infarction was established, and rats were divided into the sham, AMI and AMI + JQ1 groups. JQ1, a well-known selective BRD inhibitor, was used to suppress BET domain family activity. The mRNA and protein expression levels of BRD2, BRD3 and BRD4 were evaluated using quantitative polymerase chain reaction and western blot analysis, respectively. In addition, the expression levels of markers of cardiac damage were determined using commercial kits. The results indicated that BRD2 and BRD4 mRNA and protein expression levels were significantly increased in the AMI group compared with those in the sham group. In addition, BET inhibition decreased AMI damage in vivo by reversing cardiac function injury, decreasing serum lactate dehydrogenase and creatine kinase-MB isozyme activity, in addition to decreasing the expression levels of high-sensitivity C-reactive protein and interleukin-6. Furthermore, the results suggested that Toll-like receptor 4 (TLR4) signaling was activated by the increased expression of TLR4, TNF receptor-associated factor 6 (TRAF6) and nuclear factor (NF)-κB during AMI. However, JQ1 treatment suppressed TLR4 signaling activation. In conclusion, the present results demonstrated that the inhibition of BET family proteins suppresses AMI, and that this effect was partially mediated by the inhibition of TLR4/TRAF6/NF-κB signaling.