Published online before print November 11, 2004, doi: 10.1161/01.ATV.0000150045.27127.37
© 2005 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Role of ADAMTS-1 in Atherosclerosis
Remodeling of Carotid Artery, Immunohistochemistry, and Proteolysis of Versican
From the Department of Molecular Pharmacology (A.-C.J.-R., T.N., A.-K.A., B.R., P.B., E.H.-C, C.-H.L.-S.), Integrative Pharmacology (R.F.-D., M.B.), Molecular Science (A.T.), and Safety Assessment (A.W.), AstraZeneca R&D, Mölndal, Sweden; Arexis (J.-O.A., K.L.), Gothenburg, Sweden; and Apoteket AB (P.W.), Umeå, Sweden.
Correspondence to Chung-Hyun Lee-Søgaard, AstraZeneca, R&D, Department of Molecular Pharmacology, Pepparedsleden 1, S-431 83, Mölndal, Sweden. E-mail sogaardfamily{at}hotmail.com
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.
We investigated the potential role of ADAMTS-1 in atherogenesis. We show that ADAMTS-1 is differentially expressed in human plaques and VSMCs and that overexpression increased intimal hyperplasia in a mouse model for arterial remodeling. We hypothesize that ADAMTS-1 promotes VSMC migration and formation of neointima.
Key Words: ADAMTS-1 • atherosclerosis • versican • neointima
Related Article:
Arterioscler Thromb Vasc Biol 2005 25: 12-14.
This article has been cited by other articles:
 |
|
 |
|
  O. F. Hatipoglu, S. Hirohata, M. Z. Cilek, H. Ogawa, T. Miyoshi, M. Obika, K. Demircan, R. Shinohata, S. Kusachi, and Y. Ninomiya ADAMTS1 Is a Unique Hypoxic Early Response Gene Expressed by Endothelial Cells J. Biol. Chem., June 12, 2009; 284(24): 16325 - 16333. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Wang, J. Zheng, X. Bai, B. Liu, C.-j. Liu, Q. Xu, Y. Zhu, N. Wang, W. Kong, and X. Wang ADAMTS-7 Mediates Vascular Smooth Muscle Cell Migration and Neointima Formation in Balloon-Injured Rat Arteries Circ. Res., March 13, 2009; 104(5): 688 - 698. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Sabatine, L. Ploughman, K. L. Simonsen, O. A. Iakoubova, T. G. Kirchgessner, K. Ranade, Z. Tsuchihashi, K. E. Zerba, D. U. Long, C. H. Tong, et al. Association Between ADAMTS1 Matrix Metalloproteinase Gene Variation, Coronary Heart Disease, and Benefit of Statin Therapy Arterioscler Thromb Vasc Biol, March 1, 2008; 28(3): 562 - 567. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Blanner, R. A. Barve, and C. W. Bolten Mineralocorticoid Receptors and Vascular Inflammation: New Answers, New Questions Endocrinology, April 1, 2007; 148(4): 1498 - 1501. [Full Text] [PDF]
|
|
|
|
|
|
G. Fejes-Toth and A. Naray-Fejes-Toth Early Aldosterone-Regulated Genes in Cardiomyocytes: Clues to Cardiac Remodeling? Endocrinology, April 1, 2007; 148(4): 1502 - 1510. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-H. Chen and J. P. Walterscheid Plaque Angiogenesis Versus Compensatory Arteriogenesis in Atherosclerosis Circ. Res., October 13, 2006; 99(8): 787 - 789. [Full Text] [PDF]
|
|
|
|
|
|
V. N. Bochkov, M. Philippova, O. Oskolkova, A. Kadl, A. Furnkranz, E. Karabeg, T. Afonyushkin, F. Gruber, J. Breuss, A. Minchenko, et al. Oxidized Phospholipids Stimulate Angiogenesis Via Autocrine Mechanisms, Implicating a Novel Role for Lipid Oxidation in the Evolution of Atherosclerotic Lesions Circ. Res., October 13, 2006; 99(8): 900 - 908. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Herrmann, L. O. Lerman, D. Mukhopadhyay, C. Napoli, and A. Lerman Angiogenesis in Atherogenesis Arterioscler Thromb Vasc Biol, September 1, 2006; 26(9): 1948 - 1957. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. X. Torres-Collado, W. Kisiel, M. L. Iruela-Arispe, and J. C. Rodriguez-Manzaneque ADAMTS1 Interacts with, Cleaves, and Modifies the Extracellular Location of the Matrix Inhibitor Tissue Factor Pathway Inhibitor-2 J. Biol. Chem., June 30, 2006; 281(26): 17827 - 17837. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Uzonyi, K. Lotzer, S. Jahn, C. Kramer, M. Hildner, E. Bretschneider, D. Radke, M. Beer, R. Vollandt, J. F. Evans, et al. Cysteinyl leukotriene 2 receptor and protease-activated receptor 1 activate strongly correlated early genes in human endothelial cells PNAS, April 18, 2006; 103(16): 6326 - 6331. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. V. Lee, J. C. Rodriguez-Manzaneque, S. N.-M. Thai, W. O. Twal, A. Luque, K. M. Lyons, W. S. Argraves, and M. L. Iruela-Arispe Fibulin-1 Acts as a Cofactor for the Matrix Metalloprotease ADAMTS-1 J. Biol. Chem., October 14, 2005; 280(41): 34796 - 34804. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. N. Wight The ADAMTS Proteases, Extracellular Matrix, and Vascular Disease: Waking the Sleeping Giant(s)! Arterioscler Thromb Vasc Biol, January 1, 2005; 25(1): 12 - 14. [Full Text] [PDF]
|
|