Frontiers in Cardiovascular Medicine (May 2022)
MCC950, a Selective NLRP3 Inhibitor, Attenuates Adverse Cardiac Remodeling Following Heart Failure Through Improving the Cardiometabolic Dysfunction in Obese Mice
- Menglong Wang,
- Menglong Wang,
- Menglong Wang,
- Mengmeng Zhao,
- Mengmeng Zhao,
- Mengmeng Zhao,
- Junping Yu,
- Junping Yu,
- Junping Yu,
- Yao Xu,
- Yao Xu,
- Yao Xu,
- Jishou Zhang,
- Jishou Zhang,
- Jishou Zhang,
- Jianfang Liu,
- Jianfang Liu,
- Jianfang Liu,
- Zihui Zheng,
- Zihui Zheng,
- Zihui Zheng,
- Jing Ye,
- Jing Ye,
- Jing Ye,
- Zhen Wang,
- Zhen Wang,
- Zhen Wang,
- Di Ye,
- Di Ye,
- Di Ye,
- Yongqi Feng,
- Yongqi Feng,
- Yongqi Feng,
- Shuwan Xu,
- Shuwan Xu,
- Shuwan Xu,
- Wei Pan,
- Wei Pan,
- Wei Pan,
- Cheng Wei,
- Cheng Wei,
- Cheng Wei,
- Jun Wan,
- Jun Wan,
- Jun Wan
Affiliations
- Menglong Wang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Menglong Wang
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Menglong Wang
- Hubei Key Laboratory of Cardiology, Wuhan, China
- Mengmeng Zhao
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Mengmeng Zhao
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Mengmeng Zhao
- Hubei Key Laboratory of Cardiology, Wuhan, China
- Junping Yu
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Junping Yu
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Junping Yu
- Hubei Key Laboratory of Cardiology, Wuhan, China
- Yao Xu
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Yao Xu
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Yao Xu
- Hubei Key Laboratory of Cardiology, Wuhan, China
- Jishou Zhang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Jishou Zhang
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Jishou Zhang
- Hubei Key Laboratory of Cardiology, Wuhan, China
- Jianfang Liu
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Jianfang Liu
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Jianfang Liu
- Hubei Key Laboratory of Cardiology, Wuhan, China
- Zihui Zheng
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Zihui Zheng
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Zihui Zheng
- Hubei Key Laboratory of Cardiology, Wuhan, China
- Jing Ye
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Jing Ye
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Jing Ye
- Hubei Key Laboratory of Cardiology, Wuhan, China
- Zhen Wang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Zhen Wang
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Zhen Wang
- Hubei Key Laboratory of Cardiology, Wuhan, China
- Di Ye
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Di Ye
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Di Ye
- Hubei Key Laboratory of Cardiology, Wuhan, China
- Yongqi Feng
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Yongqi Feng
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Yongqi Feng
- Hubei Key Laboratory of Cardiology, Wuhan, China
- Shuwan Xu
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Shuwan Xu
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Shuwan Xu
- Hubei Key Laboratory of Cardiology, Wuhan, China
- Wei Pan
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Wei Pan
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Wei Pan
- Hubei Key Laboratory of Cardiology, Wuhan, China
- Cheng Wei
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Cheng Wei
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Cheng Wei
- Hubei Key Laboratory of Cardiology, Wuhan, China
- Jun Wan
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
- Jun Wan
- Cardiovascular Research Institute, Wuhan University, Wuhan, China
- Jun Wan
- Hubei Key Laboratory of Cardiology, Wuhan, China
- DOI
- https://doi.org/10.3389/fcvm.2022.727474
- Journal volume & issue
-
Vol. 9
Abstract
Obesity is often accompanied by hypertension. Although a large number of studies have confirmed that NLRP3 inhibitors can improve cardiac remodeling in mice with a normal diet, it is still unclear whether NLRP3 inhibitors can improve heart failure (HF) induced by pressure overload in obese mice. The purpose of this study was to explore the role of MCC950, a selective NLRP3 inhibitor, on HF in obese mice and its metabolic mechanism. Obese mice induced with a 10-week high-fat diet (HFD) were used in this study. After 4 weeks of HFD, transverse aortic constriction (TAC) surgery was performed to induce a HF model. MCC950 (10 mg/kg, once/day) was injected intraperitoneally from 2 weeks after TAC and continued for 4 weeks. After echocardiography examination, we harvested left ventricle tissues and performed molecular experiments. The results suggest that in obese mice, MCC950 can significantly improve cardiac hypertrophy and fibrosis caused by pressure overload. MCC950 ameliorated cardiac inflammation after TAC surgery and promoted M2 macrophage infiltration in the cardiac tissue. MCC950 not only restored fatty acid uptake and utilization by regulating the expression of CD36 and CPT1β but also reduced glucose uptake and oxidation via regulating the expression of GLUT4 and p-PDH. In addition, MCC950 affected the phosphorylation of AKT and AMPK in obese mice with HF. In summary, MCC950 can alleviate HF induced by pressure overload in obese mice via improving cardiac metabolism, providing a basis for the clinical application of NLRP3 inhibitors in obese patients with HF.
Keywords