MiRNA-34a, miRNA-145, and miRNA-222 Expression, Matrix Metalloproteinases, TNF-α and VEGF in Patients with Different Phenotypes of Coronary Artery Disease.

The development of different phenotypes of coronary artery (CA) lesions is regulated via many various factors, such as pro-inflammatory agents, zinc-dependent endopeptidases, growth factors and circulating microRNAs (miRs). To evaluate the expression levels of miR-34a, miR-145 and miR-222, tumor necrosis factor α (TNF-α), matrix metalloproteinases (MMP-1, -9, -13 and -14) and vascular endothelial growth factor (VEGF) in patients with different phenotypes of coronary artery disease (CAD): ischemia/angina with non-obstructive coronary arteries (INOCA/ANOCA) and obstructive CAD (oCAD) compared with a control group. This cross-sectional observational study included 157 subjects with a verified CAD diagnosis (51 patients with INOCA, 76 patients with oCAD and 30 healthy volunteers). The expression of miR-34a, miR-145 and miR-222 (RT-PCR) and the levels of VEGF, TNF-α, MMP-1, MMP-9, MMP-13 and MMP-14 (ELISA) were estimated in plasma samples. A higher concentration of MMP-9 was found in oCAD-group samples compared to the INOCA/ANOCA group. The INOCA/ANOCA group was characterized by higher levels of TNF-α. Based on multivariate regression analysis, a mathematical model predicting the type of CA lesion was constructed. MiR-145 was the independent predictor of INOCA/ANOCA (p = 0.006). Changes in concentrations of MMP-9 and MMP-14 were found in both investigated CAD groups, with MMP-9 levels being significantly higher in obstructive CAD samples than in INOCA/ANOCA, which confirms the role of inflammation in the development of atherosclerosis. A multivariate regression analysis allowed us to achieve a model that can predict the phenotype of stable CAD, and MiR-145 can be assumed as an independent predictor of INOCA/ANOCA.