活化T细胞核因子c1在糖尿病血管钙化进展中的作用

Role of activated T-cell cytoplasmic 1 in the progression of diabetic vascular calcification

目的探究活化T细胞核因子c1(NFATc1)在糖尿病血管钙化中的作用。方法纳入行糖尿病足截肢的患者15例,收集其血清及胫前动脉标本,根据胫前动脉钙含量分为低钙化组和高钙化组;检测患者血清和胫前动脉中NFATc1水平,分别将其与胫前动脉钙含量进行相关性分析。借助小鼠主动脉平滑肌细胞(MASMC)构建糖尿病血管钙化体外模型,检测高糖环境下MASMC的表型转分化及钙盐沉积情况。进一步利用siRNA沉默NFATc1,检测NFATc1对MASMC表型转分化和钙盐沉积的影响。结果高钙化组患者血清和胫前动脉NFATc1水平均显著高于低钙化组,且相关性分析显示血清和胫前动脉中的NFATc1都与钙含量呈正相关。在MASMC体外模型中,高糖明显减弱了MASMC收缩表型,促进其成骨表型转分化,且显著加重MASMC的钙盐沉积。高糖的促MASMC表型转分化和促钙化作用与高渗无关。在用siRNA沉默NFATc1后,MASMC的成骨样分化明显受到抑制,且钙盐沉积也显著减少。结论NFATc1可促进血管平滑肌细胞向成骨表型转分化,加速糖尿病血管钙化进展。

Aim To explore the role of activated T-cell cytoplasmic 1(NFATc1)in diabetic vascular calcification.Methods Fifteen patients with diabetic foot amputation were enrolled.Serum and anterior tibial arteries were collected.According to the calcium content of the anterior tibial arteries,patients were divided into low-calcification group and high-calcification group.The NFATc1 levels in serum and anterior tibial arteries were detected,and their correlation with the calcium content of anterior tibial arteries was analyzed respectively.An in vitro model of diabetic vascular calcification was constructed with mouse aortic smooth muscle cell(MASMC)to detect the phenotypic transition and calcium deposition of MASMC under high glucose.Furthermore,siRNA was used to silence NFATc1 to determine the effect of NFATc1 on MASMC phenotype transition and calcium deposition.Results The NFATc1 level of the highcalcification group was significantly higher than that in the low-calcification group both in serum and in anterior tibial arteries.And correlation analysis showed that the serum and anterior tibial artery NFATc1 levels were positively correlated with calcium content.In the in vitro model of MASMC,high glucose significantly weakened the contraction phenotype of MASMC,promoted the osteogenic phenotype transdifferentiation,and significantly increased the calcium deposition.The effect of high glucose in promoting phenotypic transition and promoting calcification was not connected with its hypertonicity.After silencing NFATc1 with siRNA,the osteogenic differentiation of MASMC was significantly inhibited,and calcium deposition was also significantly reduced.Conclusion NFATc1 can promote the transdifferentiation of vascular smooth muscle cell to an osteogenic phenotype and promote the progression of diabetic vascular calcification.