Differential Expression of MicroRNAs in Calcific Aortic Stenosis.

BACKGROUND

Calcific aortic stenosis (CAS) is the most common heart valve disorder. To explore the underlying mechanisms, we investigated whether key microRNAs in calcified aortic valves are differentially expressed compared to those in the non-calcified valves.

METHODS

Calcified aortic valves from patients with aortic stenosis and non-calcified aortic valves (control) from patients with aortic insufficiency (n = 8 per group) were obtained during cardiac valve replacement surgery. The expression of miR-26a, miR-939, miR-374b*, miR-214, miR-16, miR-665, miR-130a, miR-193b, and miR-602 were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). MiRanda and TargetScan programs were used to predict target genes, which were verified at the levels of mRNA and protein.

RESULTS

The expression of osteocalcin, osteopontin, Runx2, and osterix were significantly increased in the CAS group compared with the control group. The expression of miR-26a, miR-939, and miR-374b* were significantly decreased in the CAS group compared with those in the control group (p < 0.05 and p < 0.01, respectively), and the expression of miR-214 was significantly up-regulated in the CAS group compared with that in the control group (p < 0.01). No significant differences in the expression of miR-16, miR-665, miR-130a, miR-193b, and miR602 were observed between these two groups. TWIST1 was confirmed as a target for miR-214 and expression was decreased in the CAS group compared with that in the control group.

CONCLUSIONS

MiR-26a, miR-939, and miR-374b* expression was decreased and miR-214 was increased in the calcified aortic valves of CAS patients. miR-214 may promote aortic valve calcification by repressing TWIST1 expression.