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

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. 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 AMPKa (AMP-activated protein kinase a)/Nrf2 (nuclear factor E2-related factor 2)/canonical NF-?B (nuclear factor ?B) pathway, thereby reducing the infiltration of macrophages and T cells. The AMPKa/Nrf2 pathway also mediated the effects of RvE1 on VSMC phenotypic transformation and proliferation. In patients with hypertension, the serum levels of RvE1 and other eicosapentaenoic acid-derived metabolites were significantly decreased Overall design: 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.