ScholarWorks@숙명여자대학교

초록

Myocardial infarction (MI) induces ischemic damage, triggering endothelial cell (EC) dysfunction that impairs revascularization and cardiac recovery. A key contributor to this dysfunction is excessive endoplasmic reticulum (ER) stress, which is activated by MI and exacerbates EC apoptosis and impaired angiogenesis. Here we investigate the role of endothelial-specific protein arginine methyltransferase 7 (PRMT7) in mitigating ER stress and promoting vascular homeostasis after MI. We demonstrate that PRMT7 expression is upregulated in ECs under tumor necrosis factor alpha or tunicamycin treatment, while its inhibition exacerbates ER stress and induces EC death. Using endothelial-specific PRMT7-knockout models, we show that PRMT7 deficiency increases apoptosis and fibrosis, impairing cardiac recovery. Transcriptomic analysis reveals that PRMT7 loss leads to the upregulation of pro-apoptotic pathways and suppression of angiogenic and proliferative signaling. Conversely, PRMT7 overexpression or treatment with the PRMT7-inducing drug bindarit restores EC function, suppresses ER stress and enhances revascularization and cardiac repair after MI. These findings establish endothelial PRMT7 as a critical regulator of EC survival and function, highlighting its potential as a therapeutic target to mitigate ER stress and improve post-MI cardiac recovery.

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