Regenerative Medicine Research Center, Sichuan University West China Hospital, Chengdu, Sichuan 610041, China.
Tennessee Institute of Regenerative Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Exp Biol Med (Maywood). 2023 Aug;248(16):1364-1372. doi: 10.1177/15353702231194344. Epub 2023 Oct 3.
Previous studies have shown that cardiomyocytes in the subendocardial region of myocardium survive from ischemic insult. This study was undertaken to explore possible mechanisms for the survival of these cardiomyocytes, focusing on changes in endothelial cells (ECs) and blood supply. C57/B6 mice were subjected to permanent ligation of left anterior descending (LAD) coronary artery to induce myocardial ischemia (MI). The hearts were harvested at 1, 4, and 7 days post MI and examined for histological changes. It was found that the survival of cardiomyocytes was associated with a preservation of ECs in the subendocardial region, as revealed by EC-specific expression transgenic mice (). However, the EC selective proteins, PECAM1 and VEGFR2, were significantly depressed in these ECs. Consequently, the ratio of PECAM1/tdTomato was significantly decreased, indicating a transformation from PECAM1 ECs to PECAM1 ECs. Furthermore, EC junction protein, VE-cadherin, was not only depressed but also disassociated from PECAM1 in the same region. These changes led to an increase in EC permeability, as evidenced by increased blood infiltration in the subendocardial region. Thus, the increase in the permeability of ECs due to their transformation in the subendocardial region allows blood infiltration, creating a unique microenvironment and ensuring the survival of cardiomyocytes under ischemic conditions.
先前的研究表明,心肌中层的心肌细胞能够从缺血损伤中存活下来。本研究旨在探讨这些心肌细胞存活的可能机制,重点关注内皮细胞(EC)和血液供应的变化。通过结扎 C57/B6 小鼠的左前降支冠状动脉来诱导心肌缺血(MI)。在 MI 后 1、4 和 7 天采集心脏,检查组织学变化。结果发现,心肌细胞的存活与中层心肌中 EC 的保留有关,这在 EC 特异性表达转基 因小鼠()中得到证实。然而,这些 EC 中的 EC 选择性蛋白,PECAM1 和 VEGFR2,明显下调。因此,PECAM1/tdTomato 的比值显著降低,表明 PECAM1 EC 向 PECAM1 EC 的转化。此外,EC 连接蛋白 VE-cadherin 在同一区域不仅下调,而且与 PECAM1 分离。这些变化导致 EC 通透性增加,中层心肌区域的血液浸润增加。因此,由于中层心肌细胞的转化导致 EC 通透性增加,允许血液浸润,形成独特的微环境,确保心肌细胞在缺血条件下的存活。