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...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。展开更多
Acute aortic dissection(AAD) is a life-threatening cardiovascular disease caused by progressive medial degeneration of the aortic wall. A disintegrin and metalloproteinase with thrombospondin motifs 1(ADAMTS1) is a re...Acute aortic dissection(AAD) is a life-threatening cardiovascular disease caused by progressive medial degeneration of the aortic wall. A disintegrin and metalloproteinase with thrombospondin motifs 1(ADAMTS1) is a recently identified extracellular metalloproteinase participating in the development of vascular disease, such as atherosclerosis. In the present study, we found that ADAMTS1 was significantly elevated in blood samples from AAD patients compared with patients with acute myocardial infarction and healthy volunteers. Based on these findings, we established an AAD model by infusing angiotensin II in older mice. AAD was successfully developed in aorta tissues, with an incidence of 42% after 14 days in the angiotensin II group. Macrophage and neutrophil infiltration was observed in the media of the aorta, and ADAMTS1 overexpression was found in the aorta by Western blot and immunohistochemistry. Double immunofluorescence staining showed the expression of ADAMTS1 in macrophages and neutrophils. Consistent with the upregulation of ADAMTS1 in aortic dissection tissues, versican(a proteoglycan substrate of ADAMTS1) was degraded significantly more in these tissues than in control aortic tissues. These data suggest that the increased expression of ADAMTS1 protein in macrophages and neutrophils that infiltrated aortic tissues may promote the progression of AAD by degrading versican.展开更多
文摘目的: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。
基金supported by the National Natural Science Foundation of China(81170287)
文摘Acute aortic dissection(AAD) is a life-threatening cardiovascular disease caused by progressive medial degeneration of the aortic wall. A disintegrin and metalloproteinase with thrombospondin motifs 1(ADAMTS1) is a recently identified extracellular metalloproteinase participating in the development of vascular disease, such as atherosclerosis. In the present study, we found that ADAMTS1 was significantly elevated in blood samples from AAD patients compared with patients with acute myocardial infarction and healthy volunteers. Based on these findings, we established an AAD model by infusing angiotensin II in older mice. AAD was successfully developed in aorta tissues, with an incidence of 42% after 14 days in the angiotensin II group. Macrophage and neutrophil infiltration was observed in the media of the aorta, and ADAMTS1 overexpression was found in the aorta by Western blot and immunohistochemistry. Double immunofluorescence staining showed the expression of ADAMTS1 in macrophages and neutrophils. Consistent with the upregulation of ADAMTS1 in aortic dissection tissues, versican(a proteoglycan substrate of ADAMTS1) was degraded significantly more in these tissues than in control aortic tissues. These data suggest that the increased expression of ADAMTS1 protein in macrophages and neutrophils that infiltrated aortic tissues may promote the progression of AAD by degrading versican.
