Role of ADAMTS-1 in Atherosclerosis
| Autor: | Tina Nilsson, Anders Thelin, Eva Hurt-Camejo, Peter Brodin, Ann-Cathrine Jönsson-Rylander, Ann-Katrin Andersson, Anette Hammarström, Chung-Hyun Lee-Søgaard, Kerstin Lindgren, Jan-Olof Andersson, Margareta Behrendt, Pia Wallbrandt, Birgitta Rosengren, Regina Fritsche-Danielson, Annika Westin |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Neointima Pathology medicine.medical_specialty Adolescent Arteriosclerosis Carotid Artery Common Disintegrins Myocytes Smooth Muscle Muscle Smooth Vascular Cell Line Mice Versicans ADAMTS1 Protein Disintegrin Animals Humans Medicine Lectins C-Type Ligation Metalloproteinase Thrombospondin Neovascularization Pathologic biology Reverse Transcriptase Polymerase Chain Reaction business.industry Hydrolysis ADAMTS Metalloendopeptidases Anatomy Middle Aged Immunohistochemistry ADAM Proteins Mice Inbred C57BL Disease Models Animal Chondroitin Sulfate Proteoglycans biology.protein Versican Cardiology and Cardiovascular Medicine business Peptide Hydrolases |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 25:180-185 |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/01.atv.0000150045.27127.37 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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