Abstract
Background/aimsThe 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 resultsMale 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.ConclusionSac/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.
Highlights
Xueling Li and Qin Zhu contributed to this work
Mounting evidence has suggested that the beneficial impact of Sac/Val, the angiotensin receptorneprilysin inhibitor (ARNI) over standard of care exerted an improvement in the morbidity and mortality of heart failure patients, as recommended by the current American and European guidelines [8, 23]
We found that Sac/Val, as expected, significantly improved protection against cardiac functional decline in a mouse model of pressure unloading
Summary
Xueling Li and Qin Zhu contributed to this work. 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]. Left ventricular reverse remodeling following successful TAVR is incomplete and is characterized by persistent cardiac fibrosis, inflammation, and hypertrophy, leading to a poor prognosis [4]. Better strategies for promoting the recovery of early cardiac function post-TAVR are essential to delay heart failure and improve clinical outcomes
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