Is the cardioprotective effect of LCZ696 linked to increased cardiac regeneration?

Publication date: April 2019Source: Archives of Cardiovascular Diseases Supplements, Volume 11, Issue 2Author(s): A. Carboni, C. Bielmann, S. Rignault-Clerc, N. Rosenblatt-VelinLCZ696 treatment reduces the mortality and the risk of hospitalization of patients with hypertension or heart failure with a preserved ejection fraction by 20%. The LCZ696 molecule associates both an angiotensin receptor blocker (valsartan) and an inhibitor of neprilysin (NEP, sacubitril). NEP is an endopeptidase able to degrade several factors such as the natriuretic peptides, angiotensin II, bradykinin, endothelin-1.Despite the cardioprotective effect of LCZ696, its exact mechanism in the heart is not elucidated yet.The aim of this project is to determine whether a part of the cardioprotective effect of this treatment is due to the stimulation of heart regeneration.For this purpose, myocardial infarction was induced in 8–10 weeks-old C57BL/6 mice by ligature of the left anterior descending coronary artery. Mice were treated or not with LCZ696 (at 6 or 60 mg/kg) given by oral gavage once per day and sacrificed 10 days after surgery. For all mice, BrdU (1 mg/ml) was added to drinking water 1 day after surgery and during all the treatment period. The effect of the treatment on heart function, cardiomyocyte proliferation and neovascularization was evaluated.High dose of LCZ696 increases the ejection fraction (+23%) and the fractional shortening (+14%) of infarcted hearts. Heart remodeling (th...
Source: Archives of Cardiovascular Diseases Supplements - Category: Cardiology Source Type: research