Heart failure

MCC950, a Selective NLRP3 Inhibitor, Attenuates Unwanted Cardiac Remodeling After Heart Failure by Improving Cardiometabolic Dysfunction in Obese Mice

This article was originally published here

Before Cardiovascular Med. 12 May 2022;9:727474. doi: 10.3389/fcvm.2022.727474. eCollection 2022.

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 induced heart failure (HF) by pressure overload in obese mice. The aim 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 by a high-fat diet (HFD) for 10 weeks were used in this study. After 4 weeks of HFD, transverse aortic constriction (TAC) surgery was performed to induce an HF pattern. MCC950 (10 mg/kg, once/day) was injected intraperitoneally starting 2 weeks after TAC and continued for 4 weeks. After an echocardiographic examination, we removed tissue from the left ventricle and performed molecular experiments. The results suggest that in obese mice, MCC950 can significantly ameliorate cardiac hypertrophy and fibrosis caused by pressure overload. MCC950 improved cardiac inflammation after TAC surgery and promoted M2 macrophage infiltration into cardiac tissue. MCC950 not only restored fatty acid uptake and utilization by regulating CD36 and CPT1β expression, but also reduced glucose uptake and oxidation Going through regulating the expression of GLUT4 and p-PDH. Additionally, MCC950 affected AKT and AMPK phosphorylation in obese mice with HF. In summary, MCC950 can attenuate pressure overload-induced IC in obese mice Going through improve cardiac metabolism, providing a basis for the clinical application of NLRP3 inhibitors in obese patients with HF.

PMID:35647084 | CPM:PMC9133382 | DO I:10.3389/fcvm.2022.727474