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• W2608962373 abstract "Background The transition of aortic valve interstitial cells ( AVIC s) to myofibroblastic and osteoblast‐like phenotypes plays a critical role in calcific aortic valve disease progression. Several micro RNA s (miRs) are implicated in stem cell differentiation into osteoblast. We hypothesized that an epigenetic mechanism regulates valvular pro‐osteogenic activity. This study examined miR profile in AVIC s of calcified valves and identified miRs responsible for AVIC phenotypic transition. Methods and Results AVIC s were isolated from normal and diseased valves. The miR microarray analysis revealed 14 upregulated and 12 downregulated miRs in diseased AVIC s. Increased miR‐486 and decreased miR‐204 levels were associated with higher levels of myofibroblastic biomarker α‐smooth muscle actin and osteoblastic biomarkers runt‐related transcription factor 2 (Runx2) and osterix (Osx). Cotransfection of miR‐486 antagomir and miR‐204 mimic in diseased AVIC s reduced their ability to express Runx2 and Osx. The miR‐486 mimic upregulated α‐smooth muscle actin expression in normal AVIC s through the protein kinase B pathway and moderately elevated Runx2 and Osx levels. Knockdown of α‐smooth muscle actin attenuated Runx2 and Osx expression induced by miR‐486. The miR‐486 mimic and miR‐204 antagomir synergistically promoted Runx2 and Osx expression and calcium deposition in normal AVIC s and normal aortic valve tissue. Conclusions In AVIC s of calcified valves, increased levels of miR‐486 induce myofibroblastic transition to upregulate Runx2 and Osx expression and synergize with miR‐204 deficiency to elevate cellular and valvular pro‐osteogenic activity. These novel findings indicate that modulation of the epigenetic mechanism underlying valvular pro‐osteogenic activity has therapeutic potential for prevention of calcific aortic valve disease progression." @default.
• W2608962373 created "2017-05-05" @default.
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• W2608962373 date "2017-04-05" @default.
• W2608962373 modified "2023-10-16" @default.
• W2608962373 title "Altered MicroRNA Expression Is Responsible for the Pro‐Osteogenic Phenotype of Interstitial Cells in Calcified Human Aortic Valves" @default.
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• W2608962373 doi "https://doi.org/10.1161/jaha.116.005364" @default.
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