Abstract
Mesenchymal stem cells (MSCs) and their derived extracellular vesicles have been reported as promising tools for the management of heart disease. The aim of this study was to explore the function of adipose-derived MSCs (adMSCs)-derived exosomes (Exo) in the progression of myocardial infarction (MI) and the molecules involved. Mouse cardiomyocytes were treated with oxygen-glucose deprivation (OGD) to mimic an MI condition in vitro. The adMSCs-derived Exo were identified and administrated into the OGD-treated cardiomyocytes, and then the viability and apoptosis of cells, and the secretion of fibrosis- and inflammation-related cytokines in cells were determined. Differentially expressed microRNAs (miRNAs) in cells after Exo treatment were screened using a microarray analysis. The downstream molecules regulated by miR-671 were explored through bioinformatic analysis. Involvements of miR-671 and transforming growth factor beta receptor 2 (TGFBR2) in the exosome-mediated events were confirmed by rescue experiments. A murine model with MI was induced and treated with Exo for functional experiments in vivo. Compared to phosphate-buffered saline treatment, the Exo treatment significantly enhanced viability while reduced apoptosis of cardiomyocytes, and in reduced myocardial fibrosis and inflammation both in vitro and in vivo. miR-671 was significantly upregulated in cells after Exo treatment. Downregulation of miR-671 blocked the protective functions of Exo. miR-671 targeted TGFBR2 and suppressed phosphorylation of Smad2. Artificial downregulation of TGFBR2 enhanced viability of the OGD-treated cardiomyocytes. This study suggested that adMSC-derived exosomal miR-671 directly targets TGFBR2 and reduces Smad2 phosphorylation to alleviate MI-like symptoms both in vivo and in vitro.
Highlights
Acute myocardial infarction (MI) is defined as the acute myocardial injury with the clinical appearance of acute myocardial ischemia along with a rise and/or fall of cardiac troponin values [1, 2]
The adipose-derived MSCs (adMSCs) were allocated into adMSC group, NC-inhibitor group, miR671 inhibitor group
The cardiomyocytes were allocated into the following groups after corresponding transfection: Control group, NC mimic group, miR-671 mimic, oxygen-glucose deprivation (OGD) group, phosphate-buffered saline (PBS) group (OGD-induced cardiomyocytes were further treated with PBS for 24 h), Exo group (OGD-induced cardiomyocytes were further treated with Exo for 24 h), Exo-NC group (OGD-induced cardiomyocytes were further treated with Exo-NC for 24 h), Exo-inhibitor group (OGD-induced cardiomyocytes were further treated with Exo-inhibitor for 24 h), Exo-inhibitor + si-NC group (OGD-induced cardiomyocytes were treated with Exo-inhibitor for 24 h and transfected with si-NC), and Exo-inhibitor + si-transforming growth factor beta receptor 2 (TGFBR2) group (OGD-induced cardiomyocytes were treated with Exo-inhibitor for 24 h and transfected with si-TGFBR2)
Summary
Acute myocardial infarction (MI) is defined as the acute myocardial injury with the clinical appearance of acute myocardial ischemia along with a rise and/or fall of cardiac troponin values [1, 2]. MI is commonly known as “heart attack,” which induces the formation of noncontractile scar and the remodeling of left ventricular (LV) that further deteriorate cardiac function [3]. The consequential ischemic heart disease is a leading cause of disability and death worldwide [4]. The current clinical treatments for heart failure following MI are instrument implantation and drug use; the efficacy remains unsatisfactory [5]. The surgical interventions and thrombolysis may induce secondary reperfusion injury, leading to further irreversible death of cardiomyocytes [6]. Developing less-harmful and effective alternatives for MI management while limiting cardiomyocyte loss is of great significance
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
