Abstract 13568: Differential Regulation of Muscle-Enriched and Vascular-Related Micrornas During Transcoronary Passage in Patients With Myocardial Injury
MicroRNA (miRs) are small non-coding RNAs that intracellularly control gene expression by binding target mRNAs. Circulating levels of miRs have been recently proposed as biomarkers for cardiovascular disease. In order to identify the heart as a potential source for miRs released into the circulation, we measured concentration gradients across the coronary circulation for muscle-enriched (miR-133a, miR-499, miR-208a), vascular-related (miR-126, miR-92a), leukocyte-related (miR-155) and platelet-enriched (miR-223) miRs, by TaqMan PCR in EDTA-plasma simultaneously obtained from the aorta and the coronary venous sinus in patients with stable CAD (n=31) and with TnT-positive acute coronary syndromes (ACS, n=19). Circulating levels of the muscle-enriched miR-499 (>20-fold, p<0.001), miR-133a (11-fold, p<0.001) and miR-208a (5-fold, p<0.001) were significantly elevated in the aorta of patients with ACS compared to stable CAD. Circulating levels of miR-499 and miR-133a were significantly increased across the coronary circulation in ACS, suggestive of a cardiac release during myocardial injury. Indeed, miR-499 and miR-133a concentration gradients closely correlated with the extent of myocardial damage as measured by transcoronary gradients of hsTnT (r=0.956, p<0.001; r=0.825, p<0.001, respectively). In contrast, the vascular-related miR-126 was significantly (p=0.04) reduced during transcoronary passage in patients with ACS and the transcoronary concentration gradients of miR-126 were inversely related to the cardiac release of hsTnT (r=-0.756, p<0.001), indicating that transcoronary consumption is directly associated with the extent of myocardial injury. No associations with hsTnT were observed for leukocyte-associated miR155 or platelet-related miR-223. Muscle-enriched miR-499 and miR-133a are released from the heart into the coronary circulation upon myocardial injury and are closely correlated with the extent of myocardial injury. In contrast, the vascular-related miR-126 is consumed during transcoronary passage in patients with myocardial injury. The differential regulation of circulating miRs during the transcoronary passage might provide important insights to exploit their role as cardiac biomarkers.
- © 2011 by American Heart Association, Inc.