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Role of р38 мар-kinase expression in myocardial remodeling in experimental heart failure and possibilities of pharmacological actions

Liskova Yu. V.1, Stadnikov A. A.1, Salikova S. P.2
1 – State Budgetary Institution of Higher Professional Education, “Orenburg State Medical University” of the RF Ministry of Health Care, Sovetskaya 6, Orenburg 460000
2 – Federal State Government Military Educational Institution of Higher Professional Education, “S. M. Kirov Military Medical Academy” of the RF Ministry of Defense, Akademika Lebedeva 6, St. Petersburg 194044

Keywords: heart failure, р38a mitogen-activated protein kinase, remodeling, melatonin, perindopril, metoprolol

DOI: 10.18087/rhfj.2015.5.2134

Background. Р38 MAPK is one the most ancient signaling molecules participating in multiple cell processes in the heart, such as embryogenesis, physiological adaptation and pathology of the heart. However the role of p38 MAPK in development of HF is still unclear. Aim. To study p38 MAPK expression in rat LV myocardium in experimental HF (EHF) and after administration of melatonin, perindopril and metoprolol. Materials and methods. LV myocardium of Wistar male rats (n=38) was examined using methods of light microscopy, immunocytochemistry, and morphometry. EHF was modeled using the method of V.I. Inchina et al. (2000) by subcutaneous administration of 0.1 ml of 1% Mesaton solution for 14 days followed by forced swimming until exhaustion. Results. At 14 days of EHF, considerable structural and functional changes were observed, which were evident as pronounced cardiomyocyte (CMC) heteromorphism, considerable microvascular remodeling, and activated components of extracellular matrix (EM). These disorders persisted in the myocardium through 28 days of EHF with a tendency toward increases in the number, phenotypic heterogeneity and stroma volumetric density (VD) of dystrophic and atrophic CMC associated with high activity of р38 MAPKα. Rats treated with melatonin, perindopril and metoprolol for 14 days displayed reversal of pathological changes in both CMC and EM; data on the myocardial MAPKα expression were ambiguous. Conclusion. Different cardioprotective mechanisms of melatonin, perindopril and metoprolol and the role of р38 MAPKα in heart remodeling are discussed.
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Liskova Yu. V., Stadnikov A. A., Salikova S. P. Role of р38 мар-kinase expression in myocardial remodeling in experimental heart failure and possibilities of pharmacological actions. Russian Heart Failure Journal. 2015;16 (5):323–328

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