Análise dos efeitos da fotobiomodulação na fibrose cardíaca em modelo experimental de infarto do miocárdio: estudo do perfil e controle da expressão gênica

Abstract

Myocardial Infarction (MI) is an irreversible damage resulting from prolonged ischemia resulti ng from total or partial occlusion of one or more coronary arteries. Due to ischemic necrosis, in the acute phase of MI, a reabsorption of the cellular components and the extracellular matrix (MEC) is involved, which is the beginning of the tissue repair process. From this period, the deposition of the components of the new ECM, mainly collagen, in the infarcted tissue and in the transition zone into the viable tissue, culminates in the formation of the infarct scar characterizing the cardiac fibrosis, occurs. Recently, photobiomodulation (PBM) has become a therapeutic alternative by modulating various biological processes depending on the wavelength, dose and condition of the irradiated tissue. Thus, temporal changes in the molecular mechanisms that occurred in the myocardium reminiscent of coronary occlusion-i nduced infarction (CAO) and submitted to PBM were evaluated. An in silico analysis was performed using Bioinformatics tools for the verification of genes and microRNAs of the MEC composition involved in the formation of myocardial fibrosis. After searching the databases, 14 genes - Col1a1, Col3a1, MMP-1, MMP-2, MMP-9, TIMP-1, TIMP-2, TGF-β1, TNC, CT-1, Gal-3, NGAL, SPARC and OGN and 4 microRNAs - miR-1, miR-21, miR-29a and miR-133 were associated with post-MI myocardial fibrosis. The Myocardial Infarction Group (MI), and the Infarction + Laser Group (IM + Laser), when compared to the control group (Sham) presented differentially expressed genes, mainly after 3 days of CAO. In analysis of gene interaction network, we demonstrated associations in the regulation of target genes and microRNAs. The results found in this work suggest that photobiomodulation was able to reduce the formation of myocardial fibrosis especially by the modulation of ECM components genes in cardiac remodeling, opening perspectives for additional investigations on antifibrotic therapies for cardiovascular diseases. Thus, knowledge about the molecular processes involved in cardiac alterations post-i nsult verified in this study allows characterizing these markers as key genes and enables a more global understanding of the molecular dynamics of cardiac remodeling post-infarction.