Reversal Of Calcificataion Smooth Muscle Cells By Sulindac

Cardiovascular diseases have always been one of the major diseases which seriously threaten human health,and it is also the disease with the highest mortality rate in the world.Vascular calcification is a cardiovascular disease.Its main pathological manifestations are stiffness of vessel wall and decreased compliance.It can easily lead to myocardial ischemia,left ventricular hypertrophy and heart failure.It can also lead to thrombosis and plaque rupture.It is one of the important factors of high morbidity and mortality of cardiovascular and cerebrovascular diseases,as well as occurrence marker of atherosclerotic cardiovascular events,stroke and peripheral vascular diseases.Many risk factors,such as dyslipidemia,hypertension,diabetes mellitus and renal failure,may promote the occurrence of arterial calcification.Therefore,the prevention and treatment of vascular calcification has become the focal point of cardiovascular disease research.Exploring the mechanism of vascular calcification and effective drug treatment are hot topics in current research.In this research,the effects of Sulindac on calcified smooth muscle cells and its mechanism of action were studied in vitro.In this study,we mainly completed four parts of the work,the content and research results are as follows:(1)To establish a calcification model of smooth muscle cells induced by TGF-β1.TGF-β1 does not affect the activity of smooth muscle cells,but it can induce contractile smooth muscle cells to have the secretory and synthetic characteristics of osteoblast-like type.It causes smooth muscle cells to form calcium nodules,produce calcium deposition,and increase the activity of ALP.It can cause the expression of OPN,BMP2,Runx2 and other osteoblast-related proteins to be up-regulated,resulting in the overexpression of β-catenin.(2)The effect of Sulindac on the cell behavior of smooth muscle cells.The results showed that Sulindac can maintain the contractile phenotype of smooth muscle cells.1000 μM Sulindac significantly inhibits the migration of smooth muscle cells.And Sulindac has higher cell safety than atorvastatin at the same concentration.(3)Sulindac could inhibit TGF-β1-induced osteogenic differentiation of vascular smooth muscle cells.Sulindac could effectively inhibit the osteogenic differentiation of smooth muscle cells induced by TGF-β1,maintain the contractile phenotype of smooth muscle cells,inhibit the proliferation and migration of osteogenic differentiated smooth muscle cells,reduce the calcium nodules and calcium deposition,reduce the activity of ALP,and down-regulate the expression of OPN,BMP2,Runx2 and β-catenin.(4)Sulindac inhibits osteogenic differention of vascular smooth muscle cells was by causing autophagy.The results showed that 3-methyladenine,an autophagy inhibitor,can inhibit the autophagy of smooth muscle cells induced by Sulindac,and also inhibit the inhibitory effect of Sulindac on the osteogenic differentiation of smooth muscle cells induced by TGF-β1.Inhibiting autophagy can reduce the inhibition of Sulindac on calcium deposition,ALP activity,OPN and other osteogenic related proteins in osteogenic smooth muscle cells.These results reveal the mechanism by which Sulindac inhibits TGF-β1-induced osteogenic differentiation of vascular smooth muscle cells.