Arteriosclerosis, thrombosis, and vascular biology · 2004
Role of ADAMTS-1 in atherosclerosis: remodeling of carotid artery, immunohistochemistry, and proteolysis of versican.
Сравнительное исследованиеСтатьяНазвание и аннотация: Перевод пока не подготовлен
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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
Аннотация
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.
CONCLUSIONS: We hypothesize that ADAMTS-1 may promote atherogenesis by cleaving extracellular matrix proteins such as versican and promoting VSMC migration.
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.
CONCLUSIONS: We hypothesize that ADAMTS-1 may promote atherogenesis by cleaving extracellular matrix proteins such as versican and promoting VSMC migration.
Предметные рубрики MeSH
ADAM ProteinsADAMTS1 ProteinAdolescentAnimalsArteriosclerosisCarotid Artery, CommonCell LineChondroitin Sulfate ProteoglycansDisease Models, AnimalDisintegrinsHumansHydrolysisImmunohistochemistryLectins, C-TypeLigationMaleMetalloendopeptidasesMiceMice, Inbred C57BLMiddle AgedMuscle, Smooth, VascularMyocytes, Smooth MuscleNeovascularization, PathologicPeptide HydrolasesReverse Transcriptase Polymerase Chain ReactionVersicans