Role of ADAMTS-1 in Atherosclerosis: Remodeling of Carotid Artery, Immunohistochemistry, and Proteolysis of Versican

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 25; no. 1; pp. 180 - 185
• Main Authors: Jönsson-Rylander, Ann-Cathrine, Nilsson, Tina, Fritsche-Danielson, Regina, Hammarström, Anette, Behrendt, Margareta, Andersson, Jan-Olof, Lindgren, Kerstin, Andersson, Ann-Katrin, Wallbrandt, Pia, Rosengren, Birgitta, Brodin, Peter, Thelin, Anders, Westin, Annika, Hurt-Camejo, Eva, Lee-Søgaard, Chung-Hyun
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.01.2005; Hagerstown, MD Lippincott
• Subjects: ADAM Proteins; ADAMTS1 Protein; Adolescent; Animals; Arteriosclerosis - metabolism; Arteriosclerosis - pathology; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Carotid Artery, Common - chemistry; Carotid Artery, Common - pathology; Carotid Artery, Common - secretion; Carotid Artery, Common - surgery; Cell Line; Chondroitin Sulfate Proteoglycans - metabolism; Chondroitin Sulfate Proteoglycans - secretion; Disease Models, Animal; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Disintegrins - biosynthesis; Disintegrins - immunology; Disintegrins - metabolism; Disintegrins - physiology; Humans; Hydrolysis; Immunohistochemistry - methods; Lectins, C-Type; Ligation - methods; Male; Medical sciences; Metalloendopeptidases - biosynthesis; Metalloendopeptidases - immunology; Metalloendopeptidases - metabolism; Metalloendopeptidases - physiology; Mice; Mice, Inbred C57BL; Middle Aged; Muscle, Smooth, Vascular - chemistry; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - pathology; Myocytes, Smooth Muscle - chemistry; Myocytes, Smooth Muscle - metabolism; Myocytes, Smooth Muscle - pathology; Neovascularization, Pathologic - pathology; Neurosurgery; Peptide Hydrolases - metabolism; Reverse Transcriptase Polymerase Chain Reaction - methods; Skull, brain, vascular surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Versicans; Vascular disease; Immunohistochemistry; ADAMTS-1; Proteolysis; neointima; Blood vessel; Carotid; Atherosclerosis; Cardiovascular disease; versican; Circulatory system; Artery
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/01.ATV.0000150045.27127.37

OBJECTIVE—We investigated the potential role of ADAMTS-1 (a disintegrin and metalloprotease with thrombospondin motif type I) in atherogenesis. METHODS AND 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. CONCLUSION—We hypothesize that ADAMTS-1 may promote atherogenesis by cleaving extracellular matrix proteins such as versican and promoting VSMC migration.