Abstract
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. Methods: 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: 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. Conclusions: 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.
Highlights
The main function of the heart is to provide enough force to pump blood to various parts of our body so as oxygen and nutrients are provided
Results revealed that rats of group II (HF induce group) significantly (P = 0.002) showed more myocardial injury compared to rats of the control group I
Rats of group III, group IV, and group V, (HF treated groups) showed significantly (P = 0.037) less myocardial injury compared to the rats of the group II
Summary
The main function of the heart is to provide enough force to pump blood to various parts of our body so as oxygen and nutrients are provided. A defect in the function of the heart may cause critical negative consequences to the human body. Recent studies recognized p53, which is suppressing tumor formation, to have an important role in the progression of heart failure. The main function of p53 is that it induces a group of molecules that cause programmed cell death, arrest cell growth, and inhibit angiogenesis 1. Recognizing the genes that play major roles in maintaining cardiac tissue homeostasis is considered of great importance 3. The expression of p53 is maintained by cells at its minimum levels by a certain protein which is called mouse double minute 2 homolog (MDM2). Mouse double minute 2 homolog is inactivated and the enhanced p53 expression will inhibit cell division and induce programmed cell death 4. Sacubitril, after metabolism, blocks a neutral endopeptidase (neprilysin) which is responsible for terminating the action of natriuretic peptides 9
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