Tran Thi Thuy Vy, Zhang Yan, Wei Shibo, Lee Jinwoo, Jeong Yideul, Vuong Tuan Anh, Lee Sang-Jin, Ryu Dongryeol, Bae Gyu-Un, Kang Jong-Sun
Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.
Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.
Exp Mol Med. 2025 Aug 5. doi: 10.1038/s12276-025-01517-x.
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.
心肌梗死（MI）会引发缺血性损伤，触发内皮细胞（EC）功能障碍，进而损害血管再生和心脏恢复。这种功能障碍的一个关键促成因素是内质网（ER）应激过度，它由MI激活，并加剧EC凋亡和血管生成受损。在这里，我们研究内皮特异性蛋白精氨酸甲基转移酶7（PRMT7）在减轻MI后ER应激和促进血管稳态中的作用。我们证明，在肿瘤坏死因子α或衣霉素处理下，EC中PRMT7的表达上调，而其抑制会加剧ER应激并诱导EC死亡。使用内皮特异性PRMT7基因敲除模型，我们发现PRMT7缺乏会增加细胞凋亡和纤维化，损害心脏恢复。转录组分析表明，PRMT7缺失会导致促凋亡途径上调，并抑制血管生成和增殖信号。相反，PRMT7过表达或用诱导PRMT7的药物宾达利治疗可恢复EC功能，抑制ER应激，并增强MI后的血管再生和心脏修复。这些发现确立了内皮PRMT7作为EC存活和功能的关键调节因子，突出了其作为减轻ER应激和改善MI后心脏恢复的治疗靶点的潜力。
