Circulating microRNAs and Adverse Cardiovascular Outcomes in Patients With Coronary Artery Disease

Overview

Coronary artery disease (CAD) resulting from atherosclerotic obstruction of epicardial coronary arteries accounts for more than one-third of deaths in subjects over the age of 35 worldwide. The global incidence of CAD is on the rise owing to the international epidemic of obesity, type 2 diabetes and aging, all of which are potent risk factors for coronary atherosclerosis. Participants with CAD are at high risk for subsequent adverse cardiovascular (CV) events and death; it has been estimated that one out of every five CAD patients will experience at least one adverse CV event during a 5-year follow up period. There is, however, no reliable diagnostic tool to predict the risk of adverse CV events or death in participanrs with CAD. Increasing evidence suggests that miRNAs are stably present in serum, plasma, urine, saliva and other body fluids and are considered a novel class of non-invasive biomarkers for various diseases including cancer, neurodegenerative and cardiovascular diseases

Objective：To identify the novel circulating miRNA expression profiles that may serve as a sensitive and reliable biomarker to predict future adverse CV outcomes and death in patients with established CAD. Methods：The investigators propose to utilize next-generation sequencing (RNASeq) to identify the novel plasma miRNA expression signature linked to adverse CV outcomes in participanrs with CAD. The identified miRNA candidates that are predictive of adverse CV events will be validated in a larger independent cohort of CAD patients. In addition, miRNAs that are linked to adverse CV outcomes in CAD patients will be investigated mechanistically in human aortic endothelial cells to understand their functional contribution to the occurrence of adverse CV events. What is New or Innovative in this Study? This study could be one of the few studies to investigate circulating miRNAs as novel biomarkers for risk stratification and the clinical outcome prediction in patients with established CAD. This report will also demonstrate that some dysregulated circulating miRNAs might contribute to endothelial dysfunction and adverse CV events in CAD patients. Scientific or Clinical Implication of the Expected Results：The results from this study will provide a new prognostic tool to predict CV outcomes in CAD patients using plasma miRNA expression signature. It will also provide important scientific insights into the complex non-coding RNA regulatory network involved in the pathogenesis of atherosclerosis. The insights from this study may provide a unique opportunity to improve the risk assessment of adverse CV events in CAD patients by targeting theses miRNAs.