Endothelial PRMT7 prevents dysfunction, promotes revascularization and enhances cardiac recovery post-myocardial infarction

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 α 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.