OCT-derived coronary plaque morphology and transcoronary concentration gradients of vessel wall-associated microRNAs

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Introduction: Micro-RNAs (miRs) are short, noncoding RNAs that mediate posttranscriptional gene regulation and were experimentally shown to contribute to atherosclerotic plaque formation and stability. In order to establish a potential role for miRs as biomarkers to identify the presence of vulnerable coronary plaques in patients with CAD, we correlated transcoronary concentration-gradients of vessel wall-associated miRs with coronary plaque characteristics assessed by optical coherence tomography (OCT). Methods: Blood samples were simultaneously obtained from the aorta and the coronary-sinus in 37 patients. Plasma concentrations of the vascular smooth muscle-related miR-145, the endothelial-enriched miR-126, the vascular miR-34a and the endothelial- activation-related miR-92a were measured by PCR. Comprehensive evaluation of the epicardial artery vessel wall by OCT was performed to quantificate the coronary plaque burden, the status of vascular remodelling, as well as the plaque quality (extent of intramural lipid deposits, calcification, thin-cap fibroatheroma, macrophage content and intimal lacerations) along the entire vessel length of the LAD and LCX. Results: There was a significant positive correlation between coronary plaque burden and the transcoronary concentration gradients of miR-34a (r=0.60; p<0.001), miR-145 (r=0.49; p< 0.001) and miR-126 (r=0.32; p=.0.06), but not of miR-92a (r=0.09; p=0.61). Moreover miR-145 (r=0.34, p<0.01), miR-126 (r=0.41; p<0.01) and miR-34a (r=0.48; p<0.01) are correlated with the extent of macrophage density as well as with the extent of thin-cap-fibroatheroma (TCFA; r=0.36; p<0.01 for miR-145, r=0.43, p<0.01 for miR-126 and r=0.42, p<0.01 for miR-34a). In contrast, miR-92a concentrations in the coronary effluent were unrelated to atherosclerotic plaque characteristics. An increased vulnerable plaque load was associated with the release of the atheroprotective miRs miR-126 (p<0.01) and miR-34a (p<0.01) into the coronary circulation. Conclusions: The present study is the first to document an association between vulnerable plaque load in epicardial arteries and the release of atheroprotective mIRs from the vessel wall into the coronary circulation. miR-145, miR-126 and miR-34a may thus be useful circulating biomarkers to identify patients at risk for subsequent plaque rupture.