2886Cardioprotective effect of LCZ696 (sacubitril/valsartan) experimental acute myocardial infarction

Sacubitril/Valsartan Alleviates Experimental Autoimmune Myocarditis by Inhibiting Th17 Cell Differentiation Independently of the NLRP3 Inflammasome Pathway

“…According to previous studies, compared with the usage of valsartan alone, Sac/Val treatment downregulated the expression of inflammatory factors in apoE −/− mice (Zhang et al, 2019). And Sac/Val is also superior to enalapril with regard to improving survival by inhibiting the acute phase of the post-AMI inflammatory response (Ishii et al, 2017). These studies suggest that Sac/Val is a potential therapeutic option against inflammatory heart diseases.…”

“…The mice were then randomly divided into four groups, each with six mice: (i) the "Control group" received oral gavage of corn oil (1 ml kg −1 •day −1 ); (ii) the "EAM group" received subcutaneous injections of MyHC-α and oral gavage of corn oil; (iii) the "Valsartan group" received subcutaneous injections of MyHC-α and oral gavage of valsartan (10 mg kg −1 •day −1 ) dissolved in corn oil; (iv) the "Sac/Val group" received subcutaneous injections of MyHC-α and oral gavage of Sac/Val (20 mg kg −1 •day −1 ) dissolved in corn oil. Sac/val dosage was based on the maximum dose that did not lower baseline blood pressure (Ishii et al, 2017). The hearts and samples of orbital blood were collected on day 21 for further assessments prior to euthanize the mice.…”

“…Sacubitril/valsartan (Sac/Val) is an angiotensin receptor-neprilysin inhibitor (ARNI) that reduces the risk of death and hospitalization of patients with heart failure, and researches show that it is superior to angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) in alleviating heart failure (Lefer and Sharp, 2018;Velazquez et al, 2019). Moreover, an animal experiment revealed that Sac/Val treatment improved the prognosis of acute myocardial infarction (AMI) by suppressing the expression of IL-1β and IL-6, demonstrating the anti-inflammatory effect of this drug (Ishii et al, 2017). However, its effect in inflammatory diseases and the mechanism underling its anti-inflammatory pathways are not well understood.…”

Protective Effects of Sacubitril/Valsartan on Cardiac Fibrosis and Function in Rats With Experimental Myocardial Infarction Involves Inhibition of Collagen Synthesis by Myocardial Fibroblasts Through Downregulating TGF-β1/Smads Pathway

“…Also of note is that, sacubitril/valsartan was observed to inhibit myocardial fibrosis more significantly than its effects on myocardial TGF-β1 and p-Smads protein expression, which suggests that other mechanisms besides inhibition of the TGF-β1/Smads signaling pathway are involved in the cardioprotective effects of sacubitril/valsartan after myocardial infarction. In recent years, studies have found that sacubitril/valsartan can improve ventricular remodeling after myocardial infarction through other mechanisms, such as inhibiting the release of pro-inflammatory cytokines and the activity of matrix metalloproteinase-9, preventing antioxidant enzyme against degradation, and downregulating exosomal miR-181a (Ishii et al, 2017;Imran et al, 2019;Vaskova et al, 2020). More mechanistic studies are warranted to elucidate the cardioprotective effects of sacubitril/valsartan.…”

“…Accordingly, sacubitril/ valsartan has been consistently recommended by national guidelines as a preferred treatment for heart failure with reduced ejection fraction to further reduce mortality and heart failure hospitalization when patients were still symptomatic after giving ACEI or ARB treatment (Ponikowski et al, 2016;Yancy et al, 2016;Maddox et al, 2021). However, there is scarce data regarding the effect and mechanism of sacubitril/valsartan in the setting of acute myocardial infarction (von Lueder et al, 2015;Ishii et al, 2017;Torrado et al, 2018).…”