Protection of Sacubitril/Valsartan against Pathological Cardiac Remodeling by Inhibiting the NLRP3 Inflammasome after Relief of Pressure Overload in Mice
Open Access
- 1 October 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cardiovascular Drugs and Therapy
- Vol. 34 (5), 629-640
- https://doi.org/10.1007/s10557-020-06995-x
Abstract
Background/aims The persistent existence of pathological cardiac remodeling, resulting from aortic stenosis, is related to poor clinical prognosis after successful transcatheter aortic valve replacement (TAVR). Sacubitril/valsartan (Sac/Val), comprising an angiotensin receptor blocker and a neprilysin inhibitor, has been demonstrated to have a beneficial effect against pathological cardiac remodeling, including cardiac fibrosis and inflammation in heart failure. The aim of this study was to determine whether Sac/Val exerts a cardioprotective effect after pressure unloading in mice. Methods and results Male C57BL/6 J mice were subjected to debanding (DB) surgery after 8 weeks (wk) of aortic banding (AB). Cardiac function was assessed by echocardiography, which indicated a protective effect of Sac/Val after DB. After treatment with Sac/Val post DB, decreased heart weight and myocardial cell size were observed in mouse hearts. In addition, histological analysis, immunofluorescence, and western blot results showed that Sac/Val attenuated cardiac fibrosis and inflammation after DB. Finally, our data indicated that Sac/Val treatment could significantly suppress NF-kappa B signaling and NLRP3 inflammasome activation in mice after relief of pressure overload. Conclusion Sac/Val exerted its beneficial effects to prevent maladaptive cardiac fibrosis and dysfunction in mice following pressure unloading, which was at least partly due to the inhibition of NLRP3 inflammasome activation.Keywords
Funding Information
- the Medical and Health Science and Technology Project of Zhejiang Province - Youth Talent Project (2019RC018, 2019330974)
- Chinese Medicine Research Program of Zhejiang Province (2016ZB016)
- Medical Health Science and Technology Project of Zhejiang Provincial Health Commission (2017KY200)
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