Protective Effects of microRNA-200b-3p-Encapsulated Mesenchymal Stem Cells-Secreted Extracellular Vesicles on Oxidative Stress and Cardiac Function After Myocardial Infarction via Regulating BCL2l11

Objective: Extracellular vesicles (EVs) are currently a popular treatment for myocardial injury. This work was purposed to uncover the effects of mesenchymal stem cells (MSCs)-secreted EVs miR-200b-3p on oxidative stress and cardiac function after myocardial infarction (MI) through targeting Bcl-2-like protein 11 (BCL2L11). Methods: MI mice models were established. MSCs were isolated and transfected with miR-200b-3p mimic, and MSCs-EVs were isolated. miR-200b-3p-modified MSCs-EVs, along with down-regulated or up-regulated BCL2L11 were injected into MI mice. Afterwards, pathological features, collagen volume fraction, cardiomyocyte apoptosis, cardiac function and oxidative stress were assessed in MI mice. miR-200b-3p, BCL2L11, and NACHT, LRR, and PYD domains-containing protein 1 (NLRP1) expression were measured. Results: miR-200b-3p expression was decreased in MI. BCL2L11 was targeted by miR-200b-3p and bound to NLRP1. MSCs-EVs effectively improved cardiac function and suppress oxidative stress in MI mice, and miR-200b-3p-modified MSCs-EVs attenuated MI-induced injury in mice. Down-regulating BCL2L11 enhanced MSCs-EVs-mediated attenuation of MI in mice, while up-regulating BCL2L11 caused the opposite consequence. Up-regulation of BCL2L11 negated the role of miR-200b-3p-modified MSCs-EVs in MI mice. Conclusion: A summary was obtained that miR-200b-3p-encapsulated MSCs-EVs protected against MI-induced cardiac dysfunction and oxidative stress via suppressing BCL2L11. Funding: Presidential Foundation of Nanfang hospital, China (Grant No. 2019B005). Declaration of Interest: The authors declare that they have no conflicts of interest. Ethical Approval: All animals were treated following the "Guidelines for the Care and Use of Laboratory Animals", and all experiments were conducted with the guidelines of the Ethics Committee of Nanfang Hospital, Southern Medical University.