Drug Design, Development and Therapy (Oct 2023)
The Anti-Inflammatory Mediator 17(R)-Resolvin D1 Attenuates Pressure Overload-Induced Cardiac Hypertrophy and Fibrosis
Abstract
Menglong Wang,1– 3,* Wei Pan,1– 3,* Cheng Wei,1– 3,* Jianfang Liu,1– 3 Jishou Zhang,1– 3 Junping Yu,1– 3 Mengmeng Zhao,1– 3 Shuwan Xu,1– 3 Jing Ye,1– 3 Zhen Wang,1– 3 Di Ye,1– 3 Yongqi Feng,1– 3 Yao Xu,1– 3 Jun Wan1– 3 1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China; 2Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, People’s Republic of China; 3Hubei Key Laboratory of Cardiology, Wuhan, 430060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Wan; Yao Xu, Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, People’s Republic of China, Tel +86-27-88041911, Fax +86-27-88042293, Email [email protected]; [email protected]: Increased inflammation contributes to pressure overload-induced myocardial remodeling. 17(R)-Resolvin D1 (17(R)-RvD1), a potent lipid mediator derived from docosahexaenoic acid, possesses anti-inflammatory and pro-resolving properties. However, the association between 17(R)-RvD1 and pressure overload-induced cardiac hypertrophy remains unclear.Methods: Transverse aortic constriction (TAC) surgery was performed to establish a cardiac hypertrophy model. C57BL/6J mice were randomly assigned to the Sham, TAC and TAC+17(R)-RvD1 groups. 17(R)-RvD1 was injected (2 μg/kg, i.p.) before TAC surgery and once every other day after surgery for 4 weeks. The same volume of saline was injected into the mice in both Sham group and TAC group. Then, cardiac function was evaluated and heart tissues were collected for biological analysis.Results: 17(R)-RvD1 treatment attenuated TAC-induced increase in left ventricular diameter and decrease in left ventricular contractility, mitigated increased cardiomyocyte cross-sectional area, and downregulated the expression of hypertrophic genes. Besides, 17(R)-RvD1 attenuated myocardial fibrosis, as indicated by the decreased LV collagen volume and expression of fibrotic genes. In addition, 17(R)-RvD1 ameliorated the inflammatory response in cardiac tissue, as illustrated by the decreased infiltration of CD68+ macrophages and reduced production of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6. 17(R)-RvD1 treatment significantly suppressed the activation of NLRP3 inflammasome after TAC surgery, which might be responsible for the attenuation of inflammation in cardiac tissue.Conclusion: 17(R)-RvD1 attenuated pressure overload-induced cardiac hypertrophy and fibrosis, and the possible mechanism may be associated with the inhibition of NLRP3 inflammasome. 17(R)-RvD1 may serve as a potential drug for the treatment of cardiac hypertrophy.Keywords: inflammation resolution, resolvin D1, cardiac hypertrophy, NLRP3 inflammasome, transverse aortic constriction
