Resolvin E1/ChemR23 Protects Against Hypertension and Vascular Remodeling in Angiotensin II–Induced Hypertensive Mice

作者：Jishou Zhang, Zheng Yin, Yao Xu, Cheng Wei, Shanshan Peng, Mengmeng Zhao, Jianfang Liu, Shuwan Xu, Wei Pan, Zihui Zheng, Siqi Liu, Jing Ye, Juan‐Juan Qin, Jun Wan, Menglong Wang · 发表于：Hypertension · 年份：2023 · DOI：10.1161/hypertensionaha.123.21348 · 被引用次数：48 · 研究领域：Fatty Acid Research and Health、Adipokines, Inflammation, and Metabolic Diseases、Nuclear Receptors and Signaling

BACKGROUND: Inflammation plays a critical role in the development of hypertension and vascular remodeling. Resolvin E1 (RvE1), as one of the specialized proresolving lipid mediators, promotes inflammation resolution by binding with a G protein-coupled receptor, ChemR23 (chemerin receptor 23). However, whether RvE1/ChemR23 regulates hypertension and vascular remodeling is unknown. METHODS: Hypertension in mice was induced by Ang II (angiotensin II) infusion (750 ng/kg per minute), and RvE1 (2 µg/kg per day) was administered through intraperitoneal injection. Loss of ChemR23 was achieved by mice receiving intravenous injection of adeno-associated virus 9-encoding shRNA against ChemR23. RESULTS: Aortic ChemR23 expression was increased in Ang II-induced hypertensive mice and that ChemR23 was mainly expressed on vascular smooth muscle cells (VSMCs). RvE1 lowered blood pressure, reduced aortic media thickness, attenuated aortic fibrosis, and mitigated VSMC phenotypic transformation and proliferation in hypertensive mice, which were all reversed by the knockdown of ChemR23. Moreover, RvE1 reduced the aortic infiltration of macrophages and T cells, which was also reversed by ChemR23 knockdown. RvE1 inhibited Ccl5 expression in VSMCs via the AMPKα (AMP-activated protein kinase α)/Nrf2 (nuclear factor E2-related factor 2)/canonical NF-κB (nuclear factor κB) pathway, thereby reducing the infiltration of macrophages and T cells. The AMPKα/Nrf2 pathway also mediated the effects of RvE1 on...