Puerarin from Pueraria lobate attenuates ischemia-induced cardiac injuries and inflammation in vitro and in vivo: The key role of miR-130a-5p/HMGB2 pathway.

Acute myocardial infarction (AMI) is a common cardiovascular disease and puerarin (Pue) is an active compound from Pueraria lobate with cardio-protective potential. In the current study, the mechanism underlying the cardio-protective effects of Pue was explored by focusing miR-130a-5p/HMGB2 pathway. MiR expression profile was determined and myocardial infarction was induced in cardiomyocytes and rats, which was treated with Pue. The role of miR-130a-5p and downstream HMGB2/NF-κB axis in the cardio-protective effects of Pue was also explored. Pue increased viability and suppressed inflammation in OGD cardiomyocytes, which was associated with the deactivation of HMGB2/NF-κB pathway. After the suppression of miR-130a-5p, the cardio-protective effects of Pue were compromised. In rat models, Pue attenuated structure deterioration and inflammatory response in heart. At the molecular level, miR-130a-5p was up-regulated, and HMGB2 were down-regulated. It was demonstrated that Pue induced the expression of miR-130a-5p, which suppressed the activity of HMGB2/NF-κB, contributing to the attenuation of infarct heart tissues.

Exosomes derived from bone mesenchymal stem cells attenuate myocardial fibrosis both in vivo and in vitro via autophagy activation: the key role of miR-199a-3p/mTOR pathway.

Autophagy suppression plays key a role during myocardial fibrosis (MF) progression. Exosomes from stem cells attenuate MF. The current study aimed to explain the antifibrosis effects of exosomes by focusing on microRNAs (miRs). MF was induced in rats using transverse aortic constriction (TAC) method and handled with exosomes from bone mesenchymal stem cells (BMSCs). The results of in vivo assays were verified with H9c2 cells. MiR expression profile was determined using microarray detection. The influence of miR-199a-3p modulation in vivo and in vitro on the antifibrosis effect of exosomes then was assessed. Exosomes attenuated MF by inhibiting inflammation, improving tissue structure, and inhibiting fibrosis-related indicators in TAC rats, and the effects were associated with autophagy activation. In H9c2 cells, exosomes suppressed cell viability, induced cell apoptosis, inhibited fibrosis-related indicators, while and the inhibition of autophagy by 3-MA would block the effect of exosomes. Based on the microarray detection, miR-199a-3p level was selected as therapeutic target. The inhibition of miR-199a-3p impaired the antifibrosis effects of exosomes on H9c2 cells, which was associated with autophagy inhibition. Collectively, exosomes from BMSCs exerted antifibrosis effects via the distant transfer of miR-199a-3p to heart tissues, which induced autophagy by inhibiting mTOR.

Association of growth differentiation factor-15 level with adverse outcomes in patients with stable coronary artery disease: A meta-analysis.

Background and aims: Studies on the association between growth-differentiation factor-15 (GDF-15) level and adverse outcomes have yielded conflicting results in patients with stable coronary artery disease (CAD). This meta-analysis aimed to evaluate the association of baseline GDF-15 level with adverse outcomes in stable CAD patients. Methods: Two authors independently searched PubMed and Embase databases from inception to May 31, 2021 for available studies that investigated the association of baseline GDF-15 level with all-cause mortality, cardiovascular mortality, or major adverse cardiovascular events (MACEs) in stable CAD patients. Pooled multivariable adjusted hazard ratio (HR) with 95% confidence interval (CI) was calculated for the highest vs. the lowest GDF-15 level. Results: Seven studies that involved 28,765 stable CAD patients were identified and analyzed. The meta-analysis showed that the highest GDF-15 level was associated with higher risk of MACEs (HR 1.42; 95% CI 1.29-1.57; p < 0.001), cardiovascular mortality (HR 1.64: 95% CI 1.25-2.14; p < 0.001), and all-cause mortality (HR 2.01; 95% CI 1.67-2.42; p < 0.001) when compared the lowest GDF-15 level. Moreover, the values of GDF-15 level in predicting MACEs were consistently observed in each named subgroup. Conclusions: Elevated blood GDF-15 level is an independent predictor of MACEs, cardiovascular mortality, and all-cause mortality in stable CAD patients. The baseline GDF-15 level may play an important role in the risk stratification of stable CAD patients.