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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:2391.)
© 2004 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Decorin Promotes Aortic Smooth Muscle Cell Calcification and Colocalizes to Calcified Regions in Human Atherosclerotic Lesions

Jens W. Fischer; Susie A. Steitz; Pamela Y. Johnson; Allen Burke; Frank Kolodgie; Renu Virmani; Cecilia Giachelli; Thomas N. Wight

From Molekulare Pharmakologie (J.W.F.), Institut für Pharmakologie und Klinische Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Germany; the Departments of Bioengineering and Pathology (S.A.S., C.G.), University of Washington, Seattle, Wash; The Hope Heart Program at the Benaroya Research Institute at Virginia Mason (P.Y.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.

Correspondence to Thomas N. Wight, PhD, Hope Heart Program, Benaroya Research Institute at Virginia Mason, 1124 Columbia Street, Seattle, WA 98104-2046. 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 ß-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.

Calcification of atherosclerotic plaques is positively correlated with plaque burden and cardiovascular mortality. The present study demonstrates that decorin expression enhances calcification of arterial smooth muscle cells in vitro and that decorin colocalizes with calcium deposits in human atherosclerotic plaques, suggesting that decorin is a promoter of vascular calcification.

Key Words: small leucine rich proteoglycan • decorin • extracellular matrix • vascular calcification • atherosclerosis

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