Sodium Tanshinone ⅡA Sulfonate Attenuates Aortic Valve Calcification Via Regulating ER Stress Related Inflammatory Pathways

CHEN Fang; MA Fei; LIU Ya-mei; WANG Dan; SHEN Xiao-jun; WEI Qun

Abstract：Objective: To study the effects of sodium tanshinone IIA sulfonate on low density lipoprotein (ox LDL) induced porcine aortic valve interstitial cells (VICs) calcification, and its mechanisms related to endoplasmic reticulum stress (ERS). Methods: Isolated porcine aortic valve interstitial cells were indentified by optical microscope and fluorescence microscope, ox LDL were used to establish the cell model of calcification, sodium tanshinone IIA sulfonate were used as intervention after ascertain the optimal concentration by MTT, alizarin red staining, western blot and real-time fluorescence quantitative PCR assay were performed for detection of BIP, Chop, Runx2 and Osteocalcin protein, ELISA method was used to detect the expression of inflammatory cytokines in the supernatant. MCP-1 anntibodies were used to test its role in osteogenesis. Results: we successfully established the VIC model of calcification. Alizarin red staining showed that tanshinone IIA sulfonate decreased the formation of calcium nodules compared with ox LDL group. Sodium tanshinone IIA can inhibit the expression of BIP and Chop genes within the cell, and can inhibit the expression of Runx2 and Osteocalcin protein. ELISA results showed that the inhibition of IL-6, IL-8 and inflammatory factor MCP-1 were also decreased by tanshinone IIA sulfonate. However, MCP-1 antibodies had littile effect on osteogenesis. Conclusion: Sodium tanshinone IIA sulfonate can inhibit the inflammatory response and osteogenic activity VIC, and its mechanism may related to the inhibition of the ERS.