Cardiospecific microRNA plasma levels are associated with coronary plaque vulnerability

Abstract

Backgrounds: Coronary plaque rupture is considered the most important mechanism that underlies the onset of myocardial infarction and sudden death. MicroRNAs (miRNAs) are small endogenous RNAs and represent a new important class of gene regulators. Numerous studies reported altered plasma and serum levels of various miRNAs in patients with cardiovascular diseases, no data exist about the relationship between plasma miRNAs and vulnerable coronary plaque. In this study, we investigated whether plasma level of miRNAs might be a sensitive marker for the coronary plaque vulnerability. Methods: Integrated backscatter intravascular ultrasound (IB-IVUS) using a 40-MHz (motorized pullback 1 mm/s) intravascular catheter was performed in 32 consecutive patients with angina pectoris who underwent percutaneous coronary intervention. Three-dimensional analysis of IB-IVUS images was performed to determine the percentage of lipid volume (%LV) and fibrous volume (%FV). Circulating miRNAs were also measured by TaqMan polymerase chain reaction in EDTA-plasma simultaneously obtained from the periphery and the coronary sinus. Results: Muscle-enriched miRNAs (miR-133a, miR-208a, miR-499), vascular-enriched miRNAs (miR-92a, miR-100, miR-126, miR-127, miR-145), and leukocyte- and platelet-enriched miRNAs (miR-155, miR-223) were measured respectively. Plasma miR-100 level was positively correlated with %LV (r=0.49, p<0.01) and negatively correlated with %FV (r=-0.43, p<0.05). Importantly, plasma miR-100 level was higher in the coronary sinus than peripheral blood samples and was more strongly correlated with %LV (r=0.52, p<0.01) and %FV (r=-0.51, p<0.01). Plasma miR-126 was negatively correlated with %LV (r=-0.37, p<0.05). Furthermore, plasma miR-126 tended to be lower in the coronary sinus and more strongly correlated with %LV (r=-0.43, p<0.05). There are no significant correlation between %LV or %FV and plasma levels of other miRNAs. Conclusions: These results suggest that miR-100 might be released into the coronary circulation from vulnerable coronary plaque, while miR-126 might be decreased during transcoronary passage, providing interesting insight into the role of miRNAs in coronary atherosclerotic diseases.