Abstract 13441: Transcriptomic Analysis of Endothelial Colony Forming Cells From the BioHEART-CT Study to Unravel New Biomarkers for Coronary Artery Disease

Abstract

Coronary artery disease (CAD) remains the leading cause of death worldwide. There are unmet needs for the diagnosis and treatment for patients with CAD, especially those without modifiable risk factors who are suspected to be at low risk for CAD. Endothelial function has predictive value for future cardiovascular events. We previously showed that endothelial colony forming cells (ECFCs) derived from the BioHEART-CT (The BioHEART Study: Assessing Patients with Suspected Cardiovascular Disease for New Biomarkers and Risk Factors) cohort can be used as a viable tool to evaluate endothelial function in patients as these cells retain the memory of their host. Here, we aimed to characterize the transcriptomic profiles of ECFCs in non-CAD and CAD patients. Based upon our previous findings on the positive correlation between mitochondrial superoxide level and the severity of CAD, we hypothesize that the transcriptomic and functional analyses of the mitochondrial pathways are dysregulated in the ECFCs in CAD patients. RNA-sequencing was performed in ECFCs cultured from the peripheral blood of 44 patients from the BioHEART-CT cohort who had computed tomography coronary angiograms scored for coronary artery calcium (CAC) and Gensini to measure CAD severity. The cohort included 45.5% women and 54.5% men with an average age of 61.6 years. Non-CAD group was determined by a Gensini score of zero, whereas CAD group was determined by a Gensini score of greater than 5. These CAD patients had median CAC score of 266.8, with significant presence of calcified and soft plaques in their coronary arteries. Transcriptomic analysis of ECFCs showed that a total of 37 genes were upregulated and 77 genes were downregulated in the CAD patients. To investigate the functional relevance of the pathways altered in the CAD cohort, dysregulation of genes was analyzed using gene set enrichment analysis. We found that the metabolic processes, those associated with mitochondrial biogenesis, were significantly altered in the ECFCs. Our approach of using RNA-sequencing to determine the gene characteristics of CAD patients and their functional relevance to disease has the potential to unravel previously un-identified genes or biomarkers that are distinct to CAD patients.