Decorin promotes aortic smooth muscle cell calcification and colocalizes to calcified regions in human atherosclerotic lesions.
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.


RESULTS
Calcification was induced in cultured bovine aortic smooth muscle cell (BASMC) by the addition of beta-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.
Fischer
Jens W
JW
Molekulare Pharmakologie, Institut für Pharmakologie und Klinische Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Germany.
Steitz
Susie A
SA
Johnson
Pamela Y
PY
Burke
Allen
A
Kolodgie
Frank
F
Virmani
Renu
R
Giachelli
Cecilia
C
Wight
Thomas N
TN
D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D002114:Calcinosis / Q000378:metabolism*; D002417:Cattle; D058575:Decorin; D016326:Extracellular Matrix Proteins; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011509:Proteoglycans / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D014162:Transfection; D015854:Up-Regulation / Q000235:genetics
C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans