Graduate Student Sungkyunkwan University Suwon, Republic of Korea
Abstract: Vascular regeneration, encompassing angiogenesis and vasculogenesis, is crucial for cardiac repair and recovery following myocardial infarction (MI). Protein arginine methyltransferase 1 (Prmt1) is a key enzyme implicated in various cellular functions, including those within the cardiovascular system. Despite its importance, the role of Prmt1 in endothelial cells (ECs), particularly in the context of vascular regeneration, remains poorly understood. This study aimed to elucidate the role of Prmt1 in ECs during vascular regeneration by employing murine MI models, in vitro 2D systems, and human-induced pluripotent stem cell (iPSC)-derived vascular organoid (VO) models. Prmt1 expression is upregulated in ECs within the ischemic zone 7 days post-MI in both human and murine cardiac tissues. EC-specific Prmt1 depletion in MI mice worsens cardiac function, increases fibrosis, impairs angiogenesis, and disrupts redox balance. Similarly, CRISPR-Cas9-mediated Prmt1 knockdown in human iPSCs reduces sprouting, EC markers, and increases mural cell markers in VOs. Pharmacological inhibition of Prmt1 with Furamidine decreases tube formation, proliferation, and sprouting while increasing oxidative stress in hypoxia-treated ECs. These findings underscore Prmt1’s critical role in vascular regeneration and cardiac repair post-MI.
