on October 7, 2004
Published online before print October 7, 2004, doi: 10.1161/01.ATV.0000147029.63303.28
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on July 7, 2004
Accepted on September 27, 2004
Decorin Promotes Aortic Smooth Muscle Cell Calcification and Colocalizes to Calcified Regions in Human Atherosclerotic Lesions
Jens W. Fischer ;
From Molekulare Pharmakologie (J.W.F.), Institut für Pharmakologie und Klinische Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Germany; the Departments of Bioengineering and Pathology (S.S., C.G.), University of Washington, Seattle, Wash; The Hope Heart Program at the Benaroya Research Institute at Virginia Mason (P.J., T.N.W.), Seattle, Wash; and the Department of Cardiovascular Pathology (A.B., F.K.,R.V.), Armed Forces Institute of Pathology, Washington, DC.
* To whom correspondence should be addressed. E-mail: twight{at}hopeheart.org.
Objective--Ectopic calcification localized to the intima of atherosclerotic plaque is a risk marker for cardiovascular events and increases the risk of aortic dissection during angioplasty. A variety of extracellular matrix molecules such as collagen type 1, bone sialoprotein, and osteopontin are known to regulate the biomineralization of bone and ectopic vascular calcification. In the present study, it was investigated whether decorin, a small leucine-rich proteoglycan expressed in bone and atherosclerotic plaque, is involved in arterial calcification.
Methods and Results--Calcification was induced in cultured bovine aortic smooth muscle cell (BASMC) by the addition of 
-glycerophosphate or inorganic phosphate. Northern and Western analysis revealed that decorin expression was strongly upregulated in mineralizing BASMC. Furthermore, overexpression of decorin using a retroviral expression vector resulted in a 3- to 4-fold elevation of calcium deposited on the BASMC monolayer. Increased calcification in response to decorin could also be mimicked by adding exogenous decorin to the cultures. In addition, human coronary atherosclerotic lesions taken from sudden-death patients showed marked colocalization of calcium deposits with decorin.
Conclusions--Decorin induces calcification of arterial smooth muscle cell cultures and colocalizes to mineral deposition in human atherosclerotic plaque, suggesting that decorin functions as promoter of intimal calcification.
Key words: small leucine rich proteoglycan • decorin • extracellular matrix • vascular calcification • atherosclerosis
This article has been cited by other articles:
 |
|
 |
|
  E. Adiguzel, P. J Ahmad, C. Franco, and M. P Bendeck Collagens in the progression and complications of atherosclerosis Vascular Medicine, February 1, 2009; 14(1): 73 - 89. [Abstract] [PDF]
|
|
|
|
 |
|
 M. J. Duer, T. Friscic, D. Proudfoot, D. G. Reid, M. Schoppet, C. M. Shanahan, J. N. Skepper, and E. R. Wise Mineral Surface in Calcified Plaque Is Like That of Bone: Further Evidence for Regulated Mineralization Arterioscler Thromb Vasc Biol, November 1, 2008; 28(11): 2030 - 2034. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Mathew, R. J. Lund, L. R. Chaudhary, T. Geurs, and K. A. Hruska Vitamin D Receptor Activators Can Protect against Vascular Calcification J. Am. Soc. Nephrol., August 1, 2008; 19(8): 1509 - 1519. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. D. Hadfield, C. F. Rock, C. A. Inkson, S. L. Dallas, L. Sudre, G. A. Wallis, R. P. Boot-Handford, and A. E. Canfield HtrA1 Inhibits Mineral Deposition by Osteoblasts: REQUIREMENT FOR THE PROTEASE AND PDZ DOMAINS J. Biol. Chem., February 29, 2008; 283(9): 5928 - 5938. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. Burke, F. D. Kolodgie, and R. Virmani Fetuin-A, Valve Calcification, and Diabetes: What Do We Understand? Circulation, May 15, 2007; 115(19): 2464 - 2467. [Full Text] [PDF]
|
|
|
|
|
|
T. A. Dugan, V. W.-C. Yang, D. J. McQuillan, and M. Hook Decorin Modulates Fibrin Assembly and Structure J. Biol. Chem., December 15, 2006; 281(50): 38208 - 38216. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Qin, M. A. Corriere, L. M. Matrisian, and R. J. Guzman Matrix Metalloproteinase Inhibition Attenuates Aortic Calcification Arterioscler Thromb Vasc Biol, July 1, 2006; 26(7): 1510 - 1516. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Higgins, S. A. Marvel, and J. D. Morrisett Quantification of Calcification in Atherosclerotic Lesions Arterioscler Thromb Vasc Biol, August 1, 2005; 25(8): 1567 - 1576. [Abstract] [Full Text] [PDF]
|
|