Medicinal Chemistry and Pharmacology Institute, Inner Mongolia University for The Nationalities, No. 1742, Holin River Street, Tongliao, 028002, Inner Mongolia, People's Republic of China.
Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, Inner Mongolia, People's Republic of China.
Cell Tissue Res. 2022 Jul;389(1):23-40. doi: 10.1007/s00441-022-03612-1. Epub 2022 May 7.
Extracellular vesicles (EVs) derived from human bone marrow mesenchymal stem cells (BMSCs) are suggested to promote angiogenesis in a rat model of acute myocardial infarction (AMI). This study aimed to explore the underlying mechanism of BMSCs-EVs in AMI-induced heart failure (HF). BMSCs were isolated and verified, and EVs were purified and identified. After establishment of AMI-induced HF models, rats were treated with BMSCs-EVs and/or overexpressing (ov)/knocking down (kd) bone morphogenetic protein 2 (BMP2). Cardiac function, myocardial histopathological changes, angiogenesis, and vascular regeneration density were measured. Levels of pro-angiogenesis factors and cardiomyocyte apoptosis were detected. The viability and angiogenesis of hypoxic human umbilical vein endothelial cells (HUVECs) were measured. After BMSCs-EV treatment, the cardiac function of HF rats was improved, myocardial fibrosis and inflammatory cell infiltration were decreased, angiogenesis was increased, and cardiomyocyte apoptosis was inhibited. BMP2 was significantly upregulated in the myocardium. Ov-BMP2-BMSCs-EVs alleviated myocardial fibrosis and inflammatory cell infiltration, and promoted angiogenesis of HF rats, and improved the activity and angiogenesis of hypoxic HUVECs, while kd-BMP2-BMSCs-EVs showed limited protection against AMI-induced HF. BMSCs-EVs deliver BMP2 to promote angiogenesis and improve cardiac function of HF rats.
源自人骨髓间充质干细胞（BMSCs）的细胞外囊泡（EVs）被认为可促进急性心肌梗死（AMI）大鼠模型中的血管生成。本研究旨在探索 BMSCs-EVs 在 AMI 诱导的心衰（HF）中的潜在机制。分离并验证 BMSCs，并纯化和鉴定 EVs。建立 AMI 诱导的 HF 模型后，用 BMSCs-EVs 和/或过表达（ov）/敲低（kd）骨形态发生蛋白 2（BMP2）处理大鼠。测量心功能、心肌组织病理学变化、血管生成和血管再生密度。检测促血管生成因子和心肌细胞凋亡水平。测量低氧人脐静脉内皮细胞（HUVECs）的活力和血管生成。BMSCs-EV 处理后，HF 大鼠的心功能得到改善，心肌纤维化和炎症细胞浸润减少，血管生成增加，心肌细胞凋亡受到抑制。BMP2 在心肌中明显上调。ov-BMP2-BMSCs-EVs 减轻了 HF 大鼠的心肌纤维化和炎症细胞浸润，促进了 HF 大鼠的血管生成，并改善了低氧 HUVECs 的活性和血管生成，而 kd-BMP2-BMSCs-EVs 对 AMI 诱导的 HF 保护作用有限。BMSCs-EVs 传递 BMP2 以促进血管生成并改善 HF 大鼠的心功能。
