Induced Ablation of Prmt1 in Endothelial Cells Causes Endothelial Dysfunction Associated with Pulmonary Thromboembolic Hypertension

• DOI: 10.1152/physiol.2024.39.s1.2486
• Publication Date: 2024-05-21T14:57:50Z
• Authors: Thi Thuy Vy Tran; Yideul Jeong; Jong-Sun Kang
• Keywords: 0303 health sciences; 03 medical and health sciences

Endothelial cells (ECs) play vital roles in regulation of vascular homeostasis, vascular tone, leukocyte traffcking, and barrier function to ensure pulmonary function. Endothelial dysfunction is a key factor for the progression of pulmonary pathogenesis. Protein arginine methyltransferase 1 (Prmt1) catalyzes asymmetric di-methylation of substrates on arginine residues and is implicated in a variety of cellular processes, including cardiovascular function. In the current study, we examined the role of Prmt1 in endothelial function by using tamoxifen-inducible EC-specific Prmt1 ablation (KO) mice. EC-specific Prmt1 ablation in adult mice (KO) for 8 weeks led to lethality, concurrent with pulmonary hypertension and thromboembolism. The lung bulk RNA sequencing and single EC RNA sequencing analyses revealed that Prmt1 ablation increased inflammation, endothelial junction disruption, apoptosis, and fibrosis. Comprehensive analysis through bulk RNA and single cell RNA sequencing revealed that Prmt1 ablation in ECs triggers homeostatic disturbance accompanied by inflammation and endothelial dysfunction, associated with hyperactivation of NFkB and Stat signaling. In conclusion, the current study suggests that Prmt1 plays a key role in pulmonary endothelial function and vascular homeostasis via the suppression of NFkB-induced endothelial dysfunction. The National Research Foundation Grant funded by the Korean Government (MIST) (NRF-2022R1A2B5B02001482). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.