Cardiac fibroblasts secrete exosome microRNA to suppress cardiomyocyte pyroptosis in myocardial ischemia/reperfusion injury.

Molecular mechanisms underlying myocardial ischemia/reperfusion (MI/R) injury and effective strategies to treat MI/R injury are both in shortage. Although pyroptosis of cardiomyocytes and the protective role of cardiac fibroblasts (CFs) have been well recognized as targets to reduce MI/R injury and sudden cardiac death (SCD), the connection has not yet been established. Here, we showed that CFs protected cardiomyocytes against MI/R-induced injury through suppression of pyroptosis. A novel molecular mechanism underpinning this effect was further identified. Under hypoxia/reoxygenation condition, CFs were found to secrete exosomes, which contain increased level of microRNA-133a (miR-133a). These exosomes then delivered miR-133a into cardiomyocytes to target ELAVL1 and repressed cardiomyocyte pyroptosis. Based on this finding, we successfully developed a new strategy that used exosomes derived from CFs with overexpressed miR-133a to enhance the therapeutic outcomes for the MI/R injury. Overall, our results provide a novel molecular basis for understanding and treating MI/R injury, and our study also provides novel insight for the postmortem diagnosis of MI/R injury induced SCD by using exosome biomarker in forensic.

The association between soluble suppression of tumorigenicity-2 and long-term prognosis in patients with coronary artery disease: A meta-analysis.

OBJECTIVE: Findings regarding the prognostic value of soluble suppression of tumorigenecity-2 (sST2) in patients with coronary artery disease (CAD) remain inconsistent. Therefore, we conducted this meta-analysis to investigate the long-term prognostic value of sST2 in patients with CAD. METHODS: A comprehensive literature search was conducted across the PubMed, Embase, and Cochrane Library databases up to June 3, 2020. The primary outcome was major adverse cardiac events (MACEs). The secondary outcomes were all-cause mortality, cardiovascular (CV) death, heart failure (HF), and myocardial infarction (MI). Pooled estimations and 95% confidence intervals (CIs) were assessed using a random-effects model. RESULTS: Twenty-two articles that enrolled a total of 17,432 patients with CAD were included in the final analysis. CAD patients in the highest categories of baseline sST2 had a significantly higher risk of MACEs (HR: 1.42, 95% CI: 1.09-1.76), all-cause mortality (HR: 2.00, 95% CI: 1.54-2.46), and CV death (HR: 1.42, 95% CI: 1.15-1.68), HF (HR: 2.41, 95% CI: 1.87-2.94), but not that of MI (HR: 1.15, 95% CI: -0.73-3.04), than those in the lowest categories. These results were consistent when baseline sST2 was presented as continuous values in one unit increments. Moreover, subgroup analysis showed that elevated baseline sST2 levels increased the long-term risk of MACEs in the acute coronary syndrome (ACS) population (HR: 1.74, 95% CI: 1.39-2.09) but only showed a trend toward higher risk of MACEs in the non-ACS population (HR: 1.09, 95% CI: 0.87-1.30). CONCLUSIONS: The findings suggest that a higher concentration of baseline sST2 is associated with a higher risk of MACEs, all-cause mortality, CV death, and HF in patients with CAD. Elevated sST2 levels could significantly predict future MACEs in the ACS population but not in the non-ACS population.