Potential role of microRNAs for diagnosis and/or monitoring of arterial stiffness

Background: Arterial stiffness occurs during the course of atherosclerosis and can be assessed by pulse wave velocity (PWV). Circulating microRNAs (miRNAs) recently emerged as potential biomarkers for vascular remodeling. We set out to study, if circulating miRNAs are related to arterial stiffness in healthy subjects and patients with coronary artery disease (CAD). Methods: PWV was measured non-invasively by Mobil-o-Graph® in 20 healthy subjects (10 men, mean age 54±12 years) and 20 CAD patients (10 men, mean age 58±8 years). In addition, 187 miRNAs were selected based on their reported association with endothelial function/dysfunction or cardiac diseases, and analyzed by quantitative reverse transcription polymerase chain reaction. Results: In absolute numbers PWV was lower in healthy subjects than in CAD patients (7.64±1.40m/s vs. 8.13±1.31m/s), however this difference was not statistically significant (p=0.260). Of 187 miRNAs, 18 miRNAs showed significantly different expression levels between healthy subjects and CAD patients. Of these, 5 miRNAs (let-7a-5p, let-7c-5p, let-7 d-5p, let-7f-5p, miR-30b-5p) which are known to have pro-angiogenic effects correlated negatively (all r≥0.355; all p≤0.025) and one miRNA (miR-185-3p) correlated positively (r=0.316; p=0.047) with PWV. Conclusions: PWV was below the cut off for existing end organ damage in both healthy subjects and CAD patients, which is in keeping with the rather well-controlled cardiovascular risk factor profile even in our CAD patients (data not shown). Nonetheless, significant correlations were found between low miRNA expression levels of the pro-angiogenic let-7 family members and increased PWV. Furthermore, the majority of the remaining miRNAs which correlated with PWV have known protein targets which interact with the endothelium. Larger studies are needed to show whether miRNAs can be used to diagnose and/or monitor arterial stiffness.