Protection of Sacubitril/Valsartan against Pathological Cardiac Remodeling by Inhibiting the NLRP3 Inflammasome after Re
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ORIGINAL ARTICLE
Protection of Sacubitril/Valsartan against Pathological Cardiac Remodeling by Inhibiting the NLRP3 Inflammasome after Relief of Pressure Overload in Mice Xueling Li 1
&
Qin Zhu 2 & Qingcheng Wang 3 & Qinggang Zhang 1 & Yaru Zheng 1 & Lihong Wang 1 & Qinyang Jin 1
# The Author(s) 2020
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-κB 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 Sacubitril/valsartan . Cardiac remodeling . NLRP3 inflammasome . Pressure unloading
Introduction
Xueling Li and Qin Zhu contributed equally to this work. Correspondence to Qinyang Jin and Lihong Wang. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10557-020-06995-x) contains supplementary material, which is available to authorized users. * Lihong Wang [email protected] * Qinyang Jin [email protected] 1
Department of Cardiology, Zhejiang provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China
2
Department of Nephrology, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, China
3
Department of Cardiology, Hangzhou Yuhang Hospital of Traditional Chinese Medicine, Hangzhou, China
Aortic stenosis (AS) is the most common type of heart valve lesion in the expanding aged population and can induce left ventricular remodeling due to chronic pressure overload, resulting in the development of heart failure [1]. Emerging clinical trials have established transcatheter aortic valve replacement (TAVR), which exhibits lower invasiveness, risk, and all-cause mortality rate, as the main interventional treatment for AS [2, 3]. However, left ventricula
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