Apelin Is a Prototype of Novel Drugs for the Treatment of Acute Myocardial Infarction and Adverse Myocardial Remodeling

Author:

Popov Sergey V.1,Maslov Leonid N.1ORCID,Mukhomedzyanov Alexandr V.1ORCID,Kurbatov Boris K.1ORCID,Gorbunov Alexandr S.1,Kilin Michail1,Azev Viacheslav N.2ORCID,Khlestkina Maria S.3,Sufianova Galina Z.3

Affiliation:

1. Tomsk National Research Medical Center, Cardiology Research Institute, The Russian Academy of Sciences, Kyevskaya 111A, Tomsk 634012, Russia

2. Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, The Russian Academy of Sciences, Pushchino 142290, Russia

3. Department of Pharmacology, Tyumen State Medical University, Tyumen 625023, Russia

Abstract

In-hospital mortality in patients with ST-segment elevation myocardial infarction (STEMI) is 5–6%. Consequently, it is necessary to develop fundamentally novel drugs capable of reducing mortality in patients with acute myocardial infarction. Apelins could be the prototype for such drugs. Chronic administration of apelins mitigates adverse myocardial remodeling in animals with myocardial infarction or pressure overload. The cardioprotective effect of apelins is accompanied by blockage of the MPT pore, GSK-3β, and the activation of PI3-kinase, Akt, ERK1/2, NO-synthase, superoxide dismutase, glutathione peroxidase, matrix metalloproteinase, the epidermal growth factor receptor, Src kinase, the mitoKATP channel, guanylyl cyclase, phospholipase C, protein kinase C, the Na+/H+ exchanger, and the Na+/Ca2+ exchanger. The cardioprotective effect of apelins is associated with the inhibition of apoptosis and ferroptosis. Apelins stimulate the autophagy of cardiomyocytes. Synthetic apelin analogues are prospective compounds for the development of novel cardioprotective drugs.

Funder

state assignment

Publisher

MDPI AG

Subject

Pharmaceutical Science

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