© 1997 American Heart Association, Inc.
Articles |
Identification of Osteoglycin as a Component of the Vascular Matrix
Differential Expression by Vascular Smooth Muscle Cells During Neointima Formation and in Atherosclerotic Plaques
From the University of Cambridge, Department of Medicine, Addenbrooke's Hospital, and the Department of Pathology, Papworth Hospital, Cambridgeshire (N.R.B.C.), UK.
Correspondence to Dr C.M. Shanahan, Department of Medicine, Addenbrooke's Hospital (Box 157), Hills Road, Cambridge, CB2 2QQ UK. E-mail cs131{at}mole.bio.cam.ac.uk
Abstract Using differential cDNA screening, we
demonstrated that the bone-associated glycoprotein
osteoglycin was highly expressed in differentiated adult rat vascular
smooth muscle cells (VSMCs) but downregulated in VSMCs that had
undergone proliferation in vitro. Further experiments in vitro revealed
that osteoglycin gene expression was downregulated by a number of
cytokines expressed in vivo (often in association with vascular
injury) including basic fibroblast growth factor, transforming growth
factor-ß, platelet-derived growth factor, and
angiotensin II. In the normal adult rat carotid artery,
osteoglycin was expressed in both the media and adventitia. However,
osteoglycin mRNA expression was substantially increased in the
adventitia and neointima 14 days after balloon injury,
implying a role for this protein in vessel remodeling. Northern
analysis of mRNA from neonatal rat aortas demonstrated
upregulation of osteoglycin mRNA at week 2, after VSMC proliferation
had ceased and when matrix modeling was maximal. In situ hybridization
studies in human coronary arteries showed that osteoglycin mRNA
was expressed by normal medial VSMCs but was downregulated in a subset
of intimal VSMCs. Osteoglycin was not expressed in the VSMCs of
adventitial vessels but was expressed in a subset of adventitial cells.
This expression pattern contrasted with that of SM22
, a contractile
protein marker of VSMC differentiation, which was highly expressed in
the media of all vessels. These data indicate that osteoglycin is a new
marker of differentiated VSMCs and may be an essential component of the
normal vascular matrix.
Key Words: osteoglycin • leucine-rich repeat • matrix • SM22 • atherosclerosis
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