ISSN 2996-8215
International Journal of Cardiology | Vol. 9, No. 8, August 2018 | pp. 57–64
DOI: 10.46882/2018/IJC/000113
Original Research Article
Cardioprotective Effects of Sacubitril/Valsartan versus Enalapril on Adverse Structural Remodeling and Tissue Fibrosis
Jean-Pierre Dubois¹, Pierre Vigneron¹, Henri Dupont²
¹Department of Cardiology, Inserm U955, Université Paris-Est Créteil, Créteil, France
²Division of Experimental Cardiology, Centre Hospitalier Universitaire de Lyon, Lyon, France
Abstract:
Angiotensin receptor-neprilysin inhibition (ARNI) shows enhanced clinical benefits in heart failure compared to traditional angiotensin-converting enzyme inhibitors (ACEIs). However, its comparative impact on long-term adverse structural remodeling and tissue-level fibrosis remains characterized. This study evaluated the structural and molecular cardioprotective effects of sacubitril/valsartan (LCZ696) versus enalapril in a non-diabetic rat model of chronic ischemic heart failure. Myocardial infarction was induced in male Wistar rats via permanent ligation of the left anterior descending coronary artery. Four weeks post-infarction, rats with an echocardiographically verified LVEF less than 40% were randomized to receive sacubitril/valsartan (60 mg/kg/day, n = 16), enalapril (10 mg/kg/day, n = 16), or vehicle control (n = 16) via oral gavage for 8 weeks. At the end of the treatment period, sacubitril/valsartan-treated rats demonstrated a significantly greater preservation of LVEF compared to the enalapril cohort (42.4% ± 3.5% vs. 36.8% ± 3.1%, p < 0.05). Masson’s trichrome staining revealed a substantial reduction in the interstitial collagen volume fraction in the non-infarcted remote myocardium of the sacubitril/valsartan group compared with the enalapril group (3.4% ± 0.6% vs. 5.2% ± 0.8%, p < 0.01). Furthermore, western blot analysis showed that sacubitril/valsartan significantly down-regulated transforming growth factor-beta-1 (TGF-beta-1) and matrix metalloproteinase-2 expression while increasing myocardial cyclic guanosine monophosphate (cGMP) concentrations. Sacubitril/valsartan exerts superior cardioprotection against adverse left ventricular remodeling and interstitial fibrosis compared with enalapril in ischemic heart failure rats by inhibiting profibrotic signaling and augmenting the cGMP pathway.
Keywords: Heart failure, Remodeling, Sacubitril/valsartan, Enalapril, Interstitial fibrosis, Animal model
Received: May 05, 2013; Revised: June 18, 2013; Accepted: July 10, 2013; Published: August 24, 2018