Potential link between microRNA-208 and cardiovascular diseases

Abstract

Background: The application of microRNAs (miRNAs) in disease diagnosis and therapy has been the center of tremendous attention over the past few years. Regarding the molecular markers involved in the pathogenesis of cardiovascular diseases, miR-208 is closely related to myocardial hypertrophy, arrythmias, myocardial infarction, myocardial fibrosis, coronary atherosclerosis and heart failure. In this review, we focus on the regulatory mechanisms of miR-208 and its correlation with cardiovascular diseases based on available literature. Methods: We performed online search of medical literature published in an English Language Format through PubMed database over the past two decades, using a combination of text words and MeSH terms: “microRNA-208”, “miR-208”, “microRNA”, “mechanism”, “function” and “cardiovascular diseases”. The most relevant articles were selected based on a subjective appraisal of their quality and mechanistic insight that could be relevant to the regulatory molecular pathway of miR-208. Full texts of the retrieved articles were accessed. Results: In cardiac hypertrophy, overexpression of miR-208 inhibits THAP1 and myostatin. Overload exercise may decrease miR-208 expression, resulting in increased expression of SOX6, MED13, SP3, Purβ and HP1β. The miR-208-Mef2 axis induces decompensated right ventricle hypertrophy in the pulmonary hypertension rat model. Nevertheless, miR-208 inhibits p21 and NLK in myocardial infarction. Moreover, miR-208 regulates Cx40 and Cx43 in arrhythmias. Additionally, abnormal levels of miR-208 suppress L-type Ca2+ channel subunits and SERCA2, affecting the handling function of Ca2+ during atrial remodeling. A strong correlation has been established between miR-208 and cardiac fibrosis via endoglin regulation and collagen I expression. Overexpression of miR-208b inhibits the expression of COL1 and ACTA2 by inhibiting GATA4, hence hindering the progression of post-infarction myocardial fibrosis. With respect to vascular diseases, miR-208 exerts its various functions by acting on proteins associated with inflammation, endothelial apoptosis, VSMC proliferation and migration, including the PPAR, ACTA2, ROR2 and PI3K/AKT pathways. Conclusions: MiR-208 plays a pivotal role in the pathogenesis of cardiovascular diseases such as myocardial hypertrophy, myocardial infarction, arrhythmias, myocardial fibrosis and dysfunction of blood vessels. Further exploration of the potential link between miR-208 and cardiovascular diseases would provide more valuable diagnostic and therapeutic insights.