Keywords : ,،,؛sacubatril,,
Impact of Sacubitril and RAAS inhibitors on p53 expression in rat-induced heart failure. A new approach for ischemic heart disease therapy
Annals of the College of Medicine, Mosul,
2020, Volume 42, Issue 1, Pages 11-18
Background: p53 is a well-known protein that prevents cancer formation, which is recognized as the main protein in the adaptation to many harmful stimuli, like oxidative stress. Among actions of p53, studies have shown that it has an important role in the development of heart failure (HF), and arteriosclerosis. Several clinical studies were done to investigate the role of p53 in the progression of HF and with the intention to improve management of heart failure.
Objective: The purpose of this work was to investigate the mechanisms of myocardial injury that precipitates heart failure that is mediated by both β-adrenergic signaling and p53, then compare the results with administered sacubitril and angiotensin system blockers.
Thirty female albino rats were allocated into five groups; group I: served as a control group; group II: were injected with isoproterenol for HF induction; and groups III, IV, and V (HF treated groups ) whereas rats received sacubitril alone, combination of sacubitril with ramipril and combination of sacubitril with aliskiren respectively, orally on daily basis.
Results revealed that rats of group II (HF induced) were significantly (P = 0.002) showed more myocardial injury and higher nuclear p53 expression compared to rats of the control group. Furthermore, rats of group III, IV, V (HF treated groups) showed significantly (P = 0.037) less myocardial injury and significantly (P = 0.015) less nuclear p53 expression compared to rats of the group II.
It was concluded that rats received either sacubitril alone or with combination of ramipril or aliskiren for HF treatment were alleviated myocardial injury and lower nuclear p53 expression.
It was concluded that anti-p53 approach may provide a novel therapeutic strategy for human ischemic heart diseases and myocardial infarction.