Trehalose Alleviates Myocardial Ischemia/Reperfusion Injury by Inhibiting NLRP3-Mediated Pyroptosis.

Myocardial ischemia/reperfusion (I/R) injury is a pathological damage secondary to myocardial ischemia that can further aggravate tissue and organ injuries. Therefore, there is an urgent need to develop an effective approach for alleviating myocardial I/R injury. Trehalose (TRE) is a natural bioactive substance that has been shown to have extensive physiological effects in various animals and plants. However, TRE's protective effects against myocardial I/R injury remain unclear. This study aimed to evaluate the protective effect of TRE pre-treatment in mice with acute myocardial I/R injury and to explore the role of pyroptosis in this process. Mice were pre-treated with trehalose (1 mg/g) or an equivalent amount of saline solution for 7 days. The left anterior descending coronary artery was ligated in mice from the I/R and I/R + TRE groups, followed by 2-h or 24-h reperfusion after 30 min. Transthoracic echocardiography was performed to assess cardiac function in mice. Serum and cardiac tissue samples were obtained to examine the relevant indicators. We established an oxygen-glucose deprivation and re-oxygenation model in neonatal mouse ventricular cardiomyocytes and validated the mechanism by which trehalose affects myocardial necrosis via overexpression or silencing of NLRP3. TRE pre-treatment significantly improved cardiac dysfunction and reduced the infarct size in mice after I/R, accompanied by a decrease in the I/R-induced levels of CK-MB, cTnT, LDH, reactive oxygen species, pro-IL-1ß, pro-IL-18, and TUNEL-positive cells. Furthermore, TRE intervention suppressed the expression of pyroptosis-related proteins following I/R. TRE attenuates myocardial I/R injury in mice by inhibiting NLRP3-mediated caspase-1-dependent pyroptosis in cardiomyocytes.

PPARγ Regulates Macrophage Polarization by Inhibiting the JAK/STAT Pathway and Attenuates Myocardial Ischemia/Reperfusion Injury In Vivo.

This study aimed to investigate the role of PPARγ and underlying mechanisms in myocardial ischemia/reperfusion injury (IRI). IRI was surgically induced in mice and neonatal rat cardiomyocytes (NRCM) were exposed to oxygen-glucose deprivation and reoxygenation (OGD/R). Quantitative genetic analysis and western blotting were performed to assess mRNA and protein levels, respectively, of PPARγ, as well as of different inflammatory, fibrosis, and apoptosis markers in cells and tissues. PPARγ was overexpressed in the heart of mice and NRCMs by viral transfection. Apoptosis and fibrosis were detected by TUNEL and Masson's trichrome staining, respectively. Enzyme-linked immunosorbent assay was performed to detect M1 and M2 macrophage-related inflammatory factors present in mouse sera. PPARγ overexpression significantly inhibited OGD/R- and IRI-induced cardiomyocyte apoptosis and fibrosis in vitro and in vivo. Moreover, PPARγ overexpression inhibited IRI-induced secretion of M1-related proinflammatory factors, whereas it supported the secretion of M2-related anti-inflammatory factors. Notably, these events were found to be mediated by the JAK/STAT pathway. In conclusion, PPARγ regulates macrophage polarization upon IRI via the JAK/STAT pathway, which will in turn prevent myocardial apoptosis and fibrosis. Hence, PPARγ may represent a valuable target for myocardial IRI treatment.

Rehabilitation effects of circuit resistance training in coronary heart disease patients: A systematic review and meta-analysis.

BACKGROUND AND HYPOTHESIS: The rehabilitation effect of circuit resistance training in coronary heart disease (CHD) patients remains unclear. We perform this review to examine the rehabilitation effect of circuit resistance training in CHD patients and to provide a basis for the formulation of reasonable individual exercise prescriptions for CHD patients. METHODS: Randomized controlled trials (RCTs) were searched on PubMed, Web of Science, The Cochrane Library, Embase, Clinical Trials, and CNKI. About 1232 studies were identified. Nine RCTs were finally used for the present meta-analysis to determine the rehabilitation effect of circuit resistance training in CHD patients, compared to aerobic training. Individuals enrolled for the studies were at a mean age of 60.5 years old and were all CHD patients. Following the PRISMA guidelines, we extracted basic information about the study and patient characteristics, as well as measurements (e.g., the peak oxygen uptake, the body mass index [BMI], the body fat percentage, the systolic blood pressure, the total cholesterol, and triglycerides). Subsequently, this meta-analysis determined the overall effect by using standardized mean difference (SMD) and 95% confidence interval (CI). RESULTS: Compared with aerobic training, circuit resistance training significantly decrease the BMI and the body fat percentage. CONCLUSIONS: As suggested from the present meta-analysis of RCTs, circuit resistance training is effective in improving the BMI and the body fat percentage in CHD patients and may help delay the progression of CHD. CRT has the advantage of lower load in most cases with a similar effect.