IDENTIFICATION OF OSTEOGLYCIN AS A COMPONENT OF THE VASCULAR MATRIX -DIFFERENTIAL EXPRESSION BY VASCULAR SMOOTH-MUSCLE CELLS DURING NEOINTIMA FORMATION AND IN ATHEROSCLEROTIC PLAQUES

Using differential cDNA screening, we demonstrated that the bone-assoc iated glycoprotein osteoglycin was highly expressed in differentiated adult rat vascular smooth muscle cells (VSMCs) but downregulated in VS MCs 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 vasc ular injury) including basic fibroblast growth factor, transforming gr owth factor-beta, platelet-derived growth factor, and angiotensin II. In the normal adult rat carotid artery, osteoglycin was expressed in b oth 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 upre gulation of osteoglycin mRNA at week 2, after VSMC proliferation had c eased and when matrix modeling was maximal. In situ hybridization stud ies in human coronary arteries showed that osteoglycin mRNA was expres sed by normal medial VSMCs but was downregulated in a subset of intima l VSMCs. Osteoglycin was not expressed in the VSMCs of adventitial ves sels but was expressed in a subset of adventitial cells. This expressi on pattern contrasted with that of SM22 alpha, a contractile protein m arker 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 norma l vascular matrix.