Proteomic sequencing analysis in a rat model of atrial fibrosis caused by chronic intermittent hypoxia.

Abstract

Atrial fibrosis caused by long-term atrial fibrillation influences the outcomes of clinical treatment. An improved understanding of the mechanisms underlying atrial fibrillation may reveal new therapeutic targets. This study was conducted to analyze the changes in protein levels in the atrial tissue of a rat model of atrial fibrillation based on proteome sequencing. Sprague-Dawley rats were used to develop a model of atrial fibrillation induced by chronic intermittent hypoxia (CIH). Histopathological changes were detected using hematoxylin and eosin staining and Masson's staining, and immunohistochemistry and western blotting for the levels of fibrosis biomarkers. Atrial fibrosis tissue samples were also evaluated by proteome sequencing. Differentially expressed proteins (DEPs) between the CIH and control groups were evaluated in functional assay. The expression levels of several key proteins were validated using western blotting. CIH resulted in atrial fibrosis and induced atrial fibrillation. We identified 145 DEPs between the CIH and control groups. These included Myh7, Myl2, Myl3, and Atpla3, which are involved in signaling pathways related to hypertrophic cardiomyopathy, glycerolipid metabolism, and cardiac muscle contraction. Western blotting revealed the upregulation of Myh7, Myl2, and Myl3 and the downregulation of Atpla3 in the CIH group compared with the control group. These results were consistent with the sequencing results. Myh7, Myl2, Myl3, and Atpla3 may play key roles in the progression of atrial fibrillation through their involvement in cardiovascular-disease-related signaling pathways.