内脂素上调ADAMTS-4表达增加动脉粥样硬化斑块易损性的研究

Research on serum level of visfatin increases the vulnerability of atherosclerotic plaque by up-regulating ADAMTS-4 expression in macrophages

目的:探讨内脂素对冠状动脉粥样硬化(AS)斑块易损性的影响。方法:入选中日友好医院心脏科2016年1月—2017年1月间60例ST段抬高性心肌梗死(STEMI)患者,收集患者外周动脉(桡动脉或股动脉)的血样和本次导致STEMI发生的冠状动脉罪犯病变局部血样,比较外周动脉与冠状动脉罪犯病变局部内脂素及血小板反应蛋白解整合素金属肽酶-4(ADAMTS-4)的表达水平,并对两者的表达水平行相关性分析,进而通过体外细胞试验在mRNA及蛋白水平上观察内脂素对巨噬细胞中ADAMTS-4表达的作用。结果:冠状动脉罪犯病变局部内脂素及ADAMTS-4水平高于外周动脉(内脂素:15.13±6.30ng/ml vs.9.20±4.13ng/ml,P<0.001;ADAMTS-4:101.27±9.56ng/ml vs 74.36±12.43ng/ml,P<0.001),同时,冠状动脉罪犯病变局部内脂素及ADAMTS-4的表达水平成正相关(R2=0.86,P<0.001)。体外实验证实,内脂素呈时间和浓度依赖性地上调ADAMTS-4mRNA及蛋白水平的表达。结论:内脂素通过促进AS斑块内巨噬细胞ADAMTS-4的表达从而导致斑块易损性的增加。

Objective:To explore the effect of visfatin on the vulnerability of coronary atherosclerotic plaque.Methods:A total of 60 patients with ST-segment elevation myocardial infarction(STEMI)were enrolled from the department of cardiology,China-Japan Friendship Hospital between January 2016 and January 2017.Blood samples were collected from the peripheral arteries(radial artery or femoral artery)and the blood of culprit lesions in the coronary artery that caused STEMI.Visfatin and ADAMTS-4 were separately compared between the peripheral arteries and the culprit lesions in the coronary artery,and the correlation between the expression of visfatin and ADAMTS-4 of culprit lesions in the coronary artery were analyzed.Then we performed research in vitro in order to illuminate the effect of visfatin on ADAMTS-4 expression in macro-phages.Results:The levels of visfatin and ADAMTS-4 in coronary culprit lesions were significantly higher than those in peripheral arteries(15.13±6.30ng/ml vs.9.20±4.13ng/ml,P<0.001),(101.27±9.56ng/ml vs 74.36±12.43ng/ml,P<0.001).There was a significant correlation between the expression of visfatin and ADAMTS-4 in coronary culprit lesions(R'=0.86,P<0.001).Visfatin increased ADAMTS-4 mRNA and protein expression in a time-and concentration-dependent manner in vitro.Conclusion:The high expression of visfatin in the le-sion of coronary atherosclerotic plaque may lead to the increase of plaque vulnerability by increasing the ex-pression of ADAMTS-4 in the plaque.