Objectives: In calcific aortic valve disease (CAVD), the valve interstitial cells (VIC) osteogenic phenotype changes can lead to thickening and calcification of the valve leaflets，eventually lead to restricted valve movement and life-threatening. This study aims to investigate the effect and mechanism of dihydrotanshinone I (DHI) on osteogenic medium (OM) induced osteogenic phenotypic transition of porcine valve interstitial cells (PVICs), which can provide theoretical and scientific basis for clinical intervention in CAVD.
Methods and results: Immunohistochemical methods were used to detect the expression of osteogenic indicators Runx2, OPN and inflammation indicators IL-1β and p-NF-κB in valve specimens of CAVD patients(N = 3) and normal controls(N = 1). PVICs stimulated by osteoblastic medium (OM) were treated with or without DHI. CCK8, ALP and Alizarin Red S staining were used to detect cell growth and calcification, respectively. The results showed that under the treated with DHI, compared with OM, the formation of calcium nodules was reduced, and the expression of calcification-related markers Runx2 and OPN were down-regulated, which quantified by qRT-PCR and western blot. In addition, on the basis of OM induction, DHI also inhibited the phosphorylation of the NF-κB/ERK1/2 and SMAD1/5/8 signaling pathway.
Conclusion: DHI (10 μM) treatment can reverse the osteogenic phenotypic transition of PVICs induced by osteogenic medium, and the mechanism may be related to NF-κB、ERK 1/2 and Smad1/5/8 pathways.
Keywords: Calcific aortic valve disease; DHI; Osteogenic differentiation; Porcine aortic valve interstitial cells.
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