title: Role of ADAMTS-1 in atherosclerosis: remodeling of carotid artery, immunohistochemistry, and proteolysis of versican.
abstract: OBJECTIVE
  We investigated the potential role of ADAMTS-1 (a disintegrin and metalloprotease with thrombospondin motif type I) in atherogenesis.
  
  
  RESULTS
  ADAMTS-1 is expressed at the highest levels in the aorta when compared with other human tissues examined. Immunolocalization studies in human aorta and coronary artery indicate that ADAMTS-1 expression is mainly seen at low levels in the medial layer, but upregulated in the intima when plaque is present. We found that ADAMTS-1 mRNA levels are significantly higher in proliferating/migrating cultured primary aortic vascular smooth muscle cells (VSMCs) compared with resting/confluent cells. Using the mouse carotid artery flow cessation model, we show that there are differences in vessel remodeling in ADAMTS-1 transgenic/apoE-deficient mice compared with apoE deficiency alone, particularly a significant increase in intimal hyperplasia. We show that ADAMTS-1 can cleave the large versican containing proteoglycan population purified from cultured human aortic VSMCs. Finally, using versican peptide substrates, we show data suggesting that ADAMTS-1 cleaves versican at multiple sites.
  
  
  CONCLUSIONS
  We hypothesize that ADAMTS-1 may promote atherogenesis by cleaving extracellular matrix proteins such as versican and promoting VSMC migration.
authors.affiliation: Department of Molecular Pharmacology, AstraZeneca, R&D, Mölndal, Sweden.
authors.forename: Ann-Cathrine
authors.initials: AC
authors.lastname: Jönsson-Rylander
authors.forename: Tina
authors.initials: T
authors.lastname: Nilsson
authors.forename: Regina
authors.initials: R
authors.lastname: Fritsche-Danielson
authors.forename: Anette
authors.initials: A
authors.lastname: Hammarström
authors.forename: Margareta
authors.initials: M
authors.lastname: Behrendt
authors.forename: Jan-Olof
authors.initials: JO
authors.lastname: Andersson
authors.forename: Kerstin
authors.initials: K
authors.lastname: Lindgren
authors.forename: Ann-Katrin
authors.initials: AK
authors.lastname: Andersson
authors.forename: Pia
authors.initials: P
authors.lastname: Wallbrandt
authors.forename: Birgitta
authors.initials: B
authors.lastname: Rosengren
authors.forename: Peter
authors.initials: P
authors.lastname: Brodin
authors.forename: Anders
authors.initials: A
authors.lastname: Thelin
authors.forename: Annika
authors.initials: A
authors.lastname: Westin
authors.forename: Eva
authors.initials: E
authors.lastname: Hurt-Camejo
authors.forename: Chung-Hyun
authors.initials: CH
authors.lastname: Lee-Søgaard
mesh_terms: D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; D000293:Adolescent; D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism / Q000473:pathology*; D017536:Carotid Artery, Common / Q000737:chemistry / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D002460:Cell Line; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D004195:Disease Models, Animal; D019483:Disintegrins / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D006868:Hydrolysis; D007150:Immunohistochemistry / Q000379:methods*; D037181:Lectins, C-Type; D008026:Ligation / Q000379:methods; D008297:Male; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000473:pathology; D010447:Peptide Hydrolases / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D053675:Versicans
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; D019483:Disintegrins; D037181:Lectins, C-Type; C508322:VCAN protein, human; C508323:Vcan protein, mouse; D053675:Versicans; D010447:Peptide Hydrolases; D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; C103859:ADAMTS1 protein, human; D008666:Metalloendopeptidases