title: A disintegrin and metalloproteinase with thrombospondin motif 1 (ADAMTS1) expression increases in acute aortic dissection.
abstract: 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.
authors.affiliation: Department of Cardiology, China-Japan Friendship Hospital, Beijing, 100029, China.
authors.forename: Yanxiang
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Cardiology, China-Japan Friendship Hospital, Beijing, 100029, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Wu
authors.affiliation: Central Laboratory of Cardiovascular Disease, China-Japan Friendship Hospital, Beijing, 100029, China.
authors.forename: Changan
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Cardiology, China-Japan Friendship Hospital, Beijing, 100029, China.
authors.forename: Fangming
authors.initials: F
authors.lastname: Zhong
authors.affiliation: Central Laboratory of Cardiovascular Disease, China-Japan Friendship Hospital, Beijing, 100029, China.
authors.forename: Geng
authors.initials: G
authors.lastname: Li
authors.affiliation: Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Kong
authors.affiliation: Department of Cardiology, China-Japan Friendship Hospital, Beijing, 100029, China. victorzheng@sina.com.
authors.forename: Jingang
authors.initials: J
authors.lastname: Zheng
mesh_terms: D051722:ADAM Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D000071097:ADAMTS1 Protein; D000784:Aortic Dissection / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000804:Angiotensin II / Q000008:administration & dosage; D000818:Animals; D001014:Aortic Aneurysm / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009504:Neutrophils / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D053675:Versicans / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; C508323:Vcan protein, mouse; D000804:Angiotensin II; D053675:Versicans; D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; C103859:ADAMTS1 protein, human; C486323:Adamts1 protein, mouse
keywords: ADAMTS1; acute aortic dissection; angiotensin II; macrophage; neutrophil