Abstract 19476: Transcoronary Gradients of Circulating Vascular and Muscle-Derived microRNAs in Patients with Acute Coronary Syndromes
MicroRNA (miRs) are small noncoding RNAs that intracellulary control gene expression by binding target mRNAs. Recent studies showed that miRs can be released into the blood and might be suitable as biomarkers for cancer and cardiovascular diseases. We investigated whether a gradient across the coronary circulation could be identified for muscular (miR-133a, miR-208) or vascular (miR-92a, miR-126) derived miRs. Circulating miRs were measured in blood obtained from the aortic bulb (Ao) and the coronary venous sinus (CVS) of 32 patients undergoing coronary angiography for stable coronary artery disease (CAD,n=15), unstable angina/anterior NSTEMI (UA/NSTEMI, n=8) or anterior STEMI (n=9). miR were measured in EDTA-plasma and blood-derived microparticles (MP) by Taqman PCR. The plasma levels of circulating muscle-derived miRs were increased in STEMI as compared with UA/NSTEMI or CAD (p<0.05 for both). Likewise, the levels of MP miR-133a were also significantly higher (p<0.01). Importantly, in STEMI patients, both plasma and MP-derived miR-133a levels were selectively increased in the CVS resulting in a significant higher CVS/Ao ratio compared to UA/NSTEMI or CAD (both p<0.01) suggestive of transcoronary release of miR-133a. Plasma and MP-related levels of the vascular-related miR-92a (2-fold increase to UA/NSTEMI and CAD, p=0.028) and miR-126 (5-fold increase to UA/NSTEMI and 3-fold increase to CAD) were also higher in patients with STEMI. However, in contrast to the increase in muscle derived miRs across the coronary circulation, the CVS/Ao ratio of the vascular-related miR-92a (p=0.043) and miR-126 (p=0.031) was significantly reduced in patients with STEMI. In conclusion, acute coronary syndromes (ACS) are associated with a significant increase in systemic levels of circulating muscle-related and vascular miRs. The documentation of a transcoronary gradient (CVS>Ao) indicates a local myocardial release of miR-133a, whereas the inverse gradient (CVS<Ao) observed in ACS for vascular miRs suggests a local degradation or the uptake of vascular miRs along the coronary circulation. Although intriguing, further studies are needed to elucidate the mechanisms underlying the inverse transcoronary gradients of muscle-derived versus vascular miRs.
- © 2010 by American Heart Association, Inc.