biostudies-literatureHua DNational Natural Science Foundation of ChinaNational Natural Science Foundation of China (National Science Foundation of China)1441https://www.ebi.ac.uk/biostudies/studies/S-EPMC11538459biostudies-literatureUnknown7(1)The endothelium-dependent vascular injury, a primary pathological feature of angiotensin II (Ang II)-induced hypertension. This study aimed to explore the role and underlying mechanisms of G protein-coupled receptor 39 (GPR39) in the pathogenesis of Ang II-induced hypertension. For in vivo studies, GPR39 knockout (KO) mice (C57BL/6 J, male) were generated and administered Ang II for 4 weeks. GPR39 expression was upregulated in the aorta of hypertensive patients and mice. The ablation of GPR39 mitigated vascular fibrosis, augmented endothelium-dependent vasodilation, and inhibited endothelial inflammation, oxidative stress, and apoptosis in mice. Additionally, GPR39 KO decreased NOD-like receptor protein 3 (Nlrp3) gene expression in Ang II-stimulated endothelial cells. Notably, Nlrp3 activaCommunications biologyTargeting GPR39 in structure-based drug discovery reduces Ang II-induced hypertension.PMC1153845982070438Sheng YTang LCao XHua DLiu MHuang WLi PXie QXu WZhang QWu XfalseTargeting GPR39 in structure-based drug discovery reduces Ang II-induced hypertension.The endothelium-dependent vascular injury, a primary pathological feature of angiotensin II (Ang II)-induced hypertension. This study aimed to explore the role and underlying mechanisms of G protein-coupled receptor 39 (GPR39) in the pathogenesis of Ang II-induced hypertension. For in vivo studies, GPR39 knockout (KO) mice (C57BL/6 J, male) were generated and administered Ang II for 4 weeks. GPR39 expression was upregulated in the aorta of hypertensive patients and mice. The ablation of GPR39 mitigated vascular fibrosis, augmented endothelium-dependent vasodilation, and inhibited endothelial inflammation, oxidative stress, and apoptosis in mice. Additionally, GPR39 KO decreased NOD-like receptor protein 3 (Nlrp3) gene expression in Ang II-stimulated endothelial cells. Notably, Nlrp3 activa2024-01-01T00:00:00Z2024 Nov2026-06-03T05:15:27.113Z2025-04-06T10:13:41.1ZS-EPMC115384593950099810.1038/s42003-024-07132-2