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Recent evidence indicates that exosomes derived from mesenchymal stem cells (MSCs) confer protective effects against myocardial ischemia/reperfusion (I/R) injury. Exosomes are carriers of potentially protective endogenous molecules, including microRNAs (miRNAs/miRs). The current study set out to test the effects of transferring miR-182-5p from MSC-derived exosomes into myocardial cells on myocardial I/R injury. First, an I/R mouse model was developed by left anterior descending coronary artery occlusion, and myocardial cells were exposed to hypoxia/reoxygenation (H/R) for in vitro I/R model establishment. Loss- and gain-of-function experiments of miR-182-5p and GSDMD were conducted to explore the effects of miR-182-5p via MSC-derived exosomes on cell pyroptosis and viability. GSDMD was robustly expressed in I/R-injured myocardial tissues and H/R-exposed myocardial cells. GSDMD upregulation promoted H/R-induced myocardial cell pyroptosis and reduced viability, corresponding to increased lactate dehydrogenase release, reactive oxygen species production, and pyroptosis. A luciferase assay demonstrated GSDMD as a target of miR-182-5p. In addition, exosomal miR-182-5p was found to diminish GSDMD-dependent cell pyroptosis and inflammation induced by H/R. Furthermore, MSC-derived exosomes carrying miR-182-5p improved cardiac function and reduced myocardial infarction, accompanied with reduced inflammation and cell pyroptosis in vivo. Taken together, our findings suggest a cardioprotective effect of exosomal miR-182-5p against myocardial I/R injury, shedding light on an attractive therapeutic strategy.

Cadmium (Cd) is an occupational and environmental heavy metal pollutant derived from many sources that is linked to endothelial homeostasis. The endothelium is an important site of Cd deposition, while increasing evidence has revealed there is a close relationship between endothelial dysfunction and abnormal lipid metabolism. However, the effects of the alterations in lipid metabolism on endothelial cells (ECs) after Cd exposure still remain unclear. In our study, human microvascular endothelial cells (HMEC‐1) were exposed to 40‐μM Cd for 6, 12, or 24 h or 10‐, 20‐, or 40‐μM Cd for 24 h, respectively. The Cd exposure accelerated the decomposition of triglyceride (TG) and resulted in the accumulation of free fatty acids (FFAs). These changes stimulated cytotoxicity, impaired fatty acid oxidation (FAO), induced reactive oxygen species (ROS) generation, altered the mitochondrial membrane potential (MMP), and decreased the ATP content, which eventually led to endothelial dysfunction and cell death. In summary, exposure to cadmium caused endothelial dysfunction by disrupting lipid metabolism in HMEC‐1. These changes were mainly due to FFA accumulation and FAO inhibition, which further induced ROS generation and mitochondrial dysfunction. Moreover, our results provide novel insight into understanding the alterations of lipid metabolism induced by Cd exposure in ECs.

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