Endothelial progenitor cells and circulating microRNAs as possible biomarkers for coronary artery disease

Endothelial cells and their precursors, i.e., endothelial progenitor cells (EPCs), along with other cell types such as smooth muscle cells and immune cells, release or sequester microRNAs (miRNAs) that actively participate in endothelial dysfunction, smooth muscle cell proliferation, vascular inflammation, and progression of atherosclerotic plaques, ultimately contributing to the transition from stable to acute coronary syndromes. The stability of circulating miRNAs has, for many years, attracted interest in their use as biomarkers in the diagnosis and monitoring of coronary artery disease (CAD).

The study was designed to assess the association of total circulating miRNAs with endothelial dysfunction and EPC-related parameters. The study was carried out in seventy-two patients with CAD (73.2 ± 5.6 years). They were compared with eighty healthy controls (HC) (70.9 ± 5.4 years).

The lipid-lipoprotein profile including triglycerides, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), non-HDL and oxidized LDL as well as endothelium-specific variables such as nitric oxide, 3-nitrotyrosine, early EPCs and total EPCs were reduced in CAD patients (p <0.001). The lower levels of nitric oxide in CAD patients (77.60 ± 49.58 μmol/L) compared to HC (290.64 ± 151.93 μmol/L) confirmed the impairment of endothelial secretory function. Total circulating miRNA levels were three-fold higher in CAD (9.36 ± 1.48 ng/L) than in HC (3.22 ± 0.48 ng/L). For miRNA, the area under the curve (AUC) was 1.0 (sensitivity 100%, specificity 100%) with a cut-off value of 5.37 ng/L, indicating a strong discriminatory potential between CAD patients and healthy controls. However, the diagnostic performance of total circulating miRNAs (AUC = 1.0) was observed in a relatively small, single-centre cohort and should be considered exploratory, requiring confirmation in larger, independent studies.

Our study provides further evidence of complex interactions between EPCs and total circulating microRNAs in coronary artery disease. The findings suggest that circulating microRNAs, particularly in combination with EPC-related parameters, may represent promising biomarkers for clinical differentiation and characterization of endothelial dysfunction in CAD patients.