To determine the role of miRNA-30b in calcific aortic valve disease, we evaluated miRNA expression in human calcific aortic valve leaflets obtained intraoperatively. Furthermore, human valve interstitial cells were evaluated with regard to miRNA-30b expression and osteogenesis by quantitative real-time polymerase chain reaction, Western blotting, flow cytometry, and alkaline phosphatase assays.
In this study, we demonstrated that miRNA-30b attenuates bone morphogenetic protein 2-induced osteoblast differentiation by targeting Runx2, Smad1, and caspase-3. Transfection of a mimic of miRNA-30b led to decreases in alkaline phosphatase activity and expressions of Runx2, Smad1, and caspase-3. Furthermore, dual luciferase reporter assays confirmed that Runx2, Smad1, and caspase-3 are direct targets of miRNA-30b.
We demonstrated a remarkable role of miRNA-30b in calcific aortic valve disease as a regulator of human aortic valvular calcification and apoptosis through direct targeting of Runx2, Smad1, and caspase-3. Targeting of miRNA-30b could serve as a novel therapeutic strategy to limit progressive calcification in aortic stenosis.