Wang Wenjuan, Peng Xue, Zhao Li, Zhao Hongying, Gu Qianqian
Department of Geriatrics, Cangzhou Central Hospital, No. 16, Xinhua West Road, Yunhe District, Cangzhou, Hebei, 061000, China.
Curr Stem Cell Res Ther. 2023;18(2):247-259. doi: 10.2174/1574888X17666220503192941.
Acute Myocardial Infarction (AMI) has been classified as a prevalent condition threatening human health. This study sought to explore the effects of bone marrow mesenchymal stem cells (BMSCs)-extracellular vesicles (EVs) on cardiomyocyte apoptosis and autophagy induced by ischemia- hypoxia (I/H).
EVs were isolated from BMSCs using ultracentrifugation. The I/H cardiomyocyte model was established and cultured with EVs to evaluate the internalization of EVs by the cardiomyocyte line, apoptosis, proliferation, and autophagy of the cardiomyocyte line. The targeting relationship between miR-144-3p and ROCK1 was verified. EVs were isolated after transfection of BMSCs with the miR-144-3p inhibitor to evaluate the effect of miR-144-3p on the cardiomyocyte line.
After overexpression of ROCK1 in the I/H cardiomyocyte line treated with EVs, the I/H cardiomyocyte line apoptosis and autophagy were determined. BMSCs-EVs suppressed I/Hinduced apoptosis and autophagy of the cardiomyocyte line. BMSCs-EVs carried miR-144-3p into the I/H cardiomyocyte line, and the down-regulation of miR-144-3p in EVs partially inverted the suppression of apoptosis and autophagy of the I/H cardiomyocyte line induced by EVs. Our findings denoted that miR- 144-3p targeted ROCK1. Overexpression of ROCK1 partially inverted the inhibition of EVs on I/H cardiomyocyte line apoptosis and autophagy. BMSCs-EVs-derived miR-144-3p targeted ROCK1 to radically activate the PI3K/AKT/mTOR pathway.
Overall, our study elicited that BMSCs-EVs carried miR-144-3p into the I/H cardiomyocyte line to target ROCK1 and stimulate the PI3K/AKT/mTOR pathway, thus inhibiting I/H-induced cardiomyocyte line apoptosis and autophagy.
急性心肌梗死（AMI）已被归类为一种威胁人类健康的常见病症。本研究旨在探讨骨髓间充质干细胞（BMSCs）来源的细胞外囊泡（EVs）对缺血缺氧（I/H）诱导的心肌细胞凋亡和自噬的影响。
采用超速离心法从BMSCs中分离出EVs。建立I/H心肌细胞模型并用EVs进行培养，以评估心肌细胞系对EVs的摄取、心肌细胞系的凋亡、增殖和自噬情况。验证了miR-144-3p与ROCK1之间的靶向关系。用miR-144-3p抑制剂转染BMSCs后分离出EVs，以评估miR-144-3p对心肌细胞系的影响。
在用EVs处理的I/H心肌细胞系中过表达ROCK1后，测定I/H心肌细胞系的凋亡和自噬情况。BMSCs-EVs抑制了I/H诱导的心肌细胞系凋亡和自噬。BMSCs-EVs将miR-144-3p携带到I/H心肌细胞系中，EVs中miR-144-3p的下调部分逆转了EVs对I/H心肌细胞系凋亡和自噬的抑制作用。我们的研究结果表明miR-144-3p靶向ROCK1。ROCK1的过表达部分逆转了EVs对I/H心肌细胞系凋亡和自噬的抑制作用。BMSCs-EVs来源的miR-144-3p靶向ROCK1以激活PI3K/AKT/mTOR通路。
总体而言，我们的研究表明BMSCs-EVs将miR-144-3p携带到I/H心肌细胞系中，靶向ROCK1并激活PI3K/AKT/mTOR通路，从而抑制I/H诱导的心肌细胞系凋亡和自噬。
