Abstract
Acute myocardial infarction (AMI) represents a leading cause of morbidity and mortality worldwide. Extracellular vesicles (EVs) are being recognized as a promising therapeutic approach in protecting against MI. Serum is a rich source of EVs, which transports various microRNAs (miRNAs, miRs). EVs from serum have been shown beneficial for protecting against ischemia-reperfusion injury; however, their roles in AMI are unclear. In addition, whether a miRNA might be responsible for the effects of serum EVs on protecting against AMI is undetermined. Here, we demonstrated that serum EVs significantly reduced cardiomyocytes apoptosis in both cellular and mouse models of AMI, and dramatically attenuated the infarct size in mouse hearts after AMI. Inhibition of miR-21 was shown to reduce the protective effects of serum EVs in inhibiting cardiomyocytes apoptosis. miR-21 was decreased in mouse hearts after AMI, while serum EVs increased that. In addition, the programmed cell death 4 (PDCD4) expression was identified as a target gene of miR-21. Therefore, our study showed the protective effects of serum EVs on AMI, and provided a novel strategy for AMI therapy.
Highlights
Acute myocardial infarction (AMI) is one of the leading causes of morbidity and mortality worldwide, which results from coronary artery occlusion and characterized by plaque rupture-induced thrombosis and subsequent hypoxic ischemic injury (Benjamin et al, 2017)
transferase-mediated dUTP in situ nick-end labeling (TUNEL) staining showed that human serum Extracellular vesicles (EVs) reduced the number of TUNEL-positive cells in neonatal rat cardiac myocytes (NRCMs) challenged with Oxygen-Glucose Deprivation and Reperfusion (OGD/R) (Figures 1B,C), with deceased Bax/Bcl-2 and cleaved caspase-3/caspase-3 ratio as determined by western blot analysis (Figures 1D–F)
Similar results were obtained using EVs from mouse serum (Figure 2). These results suggested that human and mouse serum EVs could attenuate cardiomyocytes apoptosis induced by OGD/R
Summary
Acute myocardial infarction (AMI) is one of the leading causes of morbidity and mortality worldwide, which results from coronary artery occlusion and characterized by plaque rupture-induced thrombosis and subsequent hypoxic ischemic injury (Benjamin et al, 2017). Cardiomyocytes apoptosis occurs frequently during the pathological process of AMI, leading to cardiomyocytes loss (Palojoki et al, 2001; Nabel and Braunwald, 2012). Approaches that inhibit cardiomyocytes apoptosis are promising therapeutic approach for ischemic heart injury and AMI. Extracellular vesicles (EVs) are being recognized as new candidates with emerging roles in promoting cardiac repair during AMI (Boulanger et al, 2017). EVs are extracellular membranebound vesicles (∼40–100 nm in diameter), secreted by most cell types (Simons and Raposo, 2009; Mathivanan et al, 2010). EVs contain RNAs, proteins, and lipids, some of which are specific
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