Effect And Mechanism Of Gap Junction On Warfarin Induced Vascular Calcification In Rats

Background:Vascular calcification plays a key role in the pathophysiology of coronary artery disease,ischemic stroke,and peripheral arterial disease.Commonly recognized risk factors for vascular calcification include hypertension,diabetes,increasing age,chronic kidney disease,cigarette smoking and systemic inflammation.The vitamin K antagonist,warfarin,is the most commonly prescribed oral anticoagulant,This increase in vascular calcification is due to inhibit the formation of the enzyme matrix Gla protein(MGP).So far,the mechanism of VC has not been studied thoroughly,therefore,there are few effective methods to cure AC in clinical.At present,more and more scholars think that VC is the result of vascular smooth muscle cells(VSMCs)lose their contractile ability and differentiate into osteoblast-type cells.Gap Junction(GJ)is a intercellular communication which distribute in a variety of tissue cells,it play an important role in the transmission of chemical information,coordination of cell metabolism,regulation of cell growth and differentiation,moreover,the transform-ation of VSMCs phenotype is directly affected by GJ mediated intercellular communication.In this study,we investigated the role of GJ in the pathogenesis of vascular calcification.Methods:The rats were randomly divided into three groups,respectively: control group,model group,carbenoxolone(CBX)group,A rat model of VC was generated by treating rats with a combination of warfarin and vitamin K1,the CBX group were treated with CBX on the basis of the model group,At the end of the experiments,aortic arteries were isolated for the examination of calcification morphology,calcium content,mRNA and protein expression of Cx43,α-SMactin and Runx2.Results:1、no black particles were observed in the control group,but a lot of black particles were observed in the model group,and in the CBX group the number of black particles is between control group and model group.2、the calcium contents of the model group were significantly higher than the control group(P<0.05),and The calcium deposition contents in the CBX group was significantly lower than that in the model group(P<0.05).3、the results showed warfarin increased the activity of ALP,while treated with CBX the activity of ALP was significant decreased.4、Compared with the control group,warfarin can significantly enhance the expression of Cx43,Runx2 mRNA and protein(P<0.05),after joining CBX,compared with the model group the expression of Cx43,Runx2 mRNA and protein decreased significantly(P<0.05),while α-SMactin was opposite.Conclusions:We conclude that CBX suppresses VC by lowering the expression of Cx43,and by inhibiting the differentiation of VSMC in rat aortic arteries.