Abstract 15280: Differential Release Mechanisms of Muscle-Enriched miRNAs Upon Ischemic Myocardial Injury: Insights from Transcoronary Gradient Measurements
Introduction: Micro-RNAs (miRs) act as intracellular mediators in a variety of pathophysiological processes. Recent studies demonstrated that circulating miRs may serve as blood-based biomarkers for cardiac injury. Since the stability of miRs in blood depends on their packaging into microvesicales or their incorporation into protein-complexes, we measured the release of microvesicale-associated or protein-complex-associated miRs into the coronary circulation in patients with CAD with or without myocardial injury.
Methods/Results: Blood was simultaneously obtained from the aorta and the coronary sinus during cardiac catheterization in a total of 102 patients (pts) and circulating miRs were measured by PCR in either total EDTA-plasma or in the microvesicle fraction. High-sensitive troponin T (hsTrop) measured in the coronary sinus blood was used to quantificate myocardial injury. In the coronary sinus, the muscle-enriched miRs, miR-499 and miR-133a, were significantly (p<0.001) increased in pts. with elevated hsTrop levels, and there was a positive correlation of total miR-499 (r=0.72, p<0.001) as well as total miR-133a concentrations (r=0.68; p<0.0001) with hsTrop levels. However, the microvesicle-associated concentrations of circulating miRs did only correlate with hsTrop for miR-499 (r=0.65; P<0.001), but not for miR-133a (r=0.1; p=0.3). In fact, the increased concentrations of miR-133a in the coronary sinus in pts. with elevated hsTrop was exclusively driven by non-microvesicle-associated miR-133a, whereas miR-499 was predominantly found in the microvesicle fraction of the blood. Both, the vascular-related miR-92a as well as the leukocyte-related miR-155 did not show any correlation with hsTrop indicating that the release of muscle-specific-miRs is specific for myocardial injury.
Conclusions: The muscle-enriched miR-133a and miR-499 are released into the coronary circulation upon myocardial injury and their circulating-levels correlate with the extent of myocardial damage in pts. with ACS. However, while circulating miR-499 is found in the microvesicle fraction, miR-133a is mostly protein-band indicating differential release mechanisms, which may affect their usefulness as circulating cardiac biomarkers.
- © 2012 by American Heart Association, Inc.