Clinical value and regulatory role of miR-4446-3p in coronary heart disease

Abstract

Coronary heart disease (CHD) poses a major threat to global health due to its high incidence and mortality. This study aims to investigate the role of miR-4446-3p in CHD and its potential regulatory mechanisms. The research enrolled 103 CHD patients and 91 healthy volunteers (HV). CHD patients were stratified into MACE and non-MACE groups after 1 year of follow-up. The relative expression and diagnostic value of miR-4446-3p in CHD were analyzed. The correlation of miR-4446-3p with clinical indicators of myocardial injury was investigated. The potential of miR-4446-3p as a predictor for MACE risk after surgical intervention was evaluated. The effects of miR-4446-3p knockdown on endothelial cell proliferation, apoptosis, inflammatory response, oxidative stress, and endothelial dysfunction were examined. Additionally, the interaction between miR-4446-3p and ABCG1 was verified. miR-4446-3p was markedly elevated in CHD patients. miR-4446-3p showed significant positive correlations with clinical indicators reflecting CHD severity, such as cTnI, CK-MB, NT-proBNP, and Gensini score. Furthermore, miR-4446-3p demonstrated excellent predictive performance for the occurrence of CHD and the risk of postoperative MACE. Downregulation of miR-4446-3p enhanced endothelial cell proliferation, alleviated associated inflammation and oxidative stress, and ameliorated endothelial dysfunction. Additionally, miR-4446-3p targets and regulates ABCG1, and both factors jointly influence the malignant progression of CHD. miR-4446-3p is a promising biomarker for predicting CHD occurrence and postoperative MACE risk. miR-4446-3p may promote adverse progression of CHD by targeting ABCG1.