Osteoprotegerin (OPG) is a secreted protein of the tumor necrosis factor receptor family,whichregulates bone mass by inhibiting osteoclast differentiation and activation.Although OPG is expressed ubiquitouslyand abundantly in many tissues and cell types including vascular cells,the role of OPG in other tissues is unknown.Our previous studies demonstrated that OPG was highly expressed in vascular smooth muscle cells (VSMC) andupregulated during vascular lesion formation.Methods and Results We documented,by Northern blot analysis,that the expression of OPG was more prevalent in the aorta and cultured VSMC from spontaneously hypertensive rats(SHR) compared to Wistar-Kyoto rats (WKY).In addition,we found that the expression of Angiotensin Ⅱ (Ang Ⅱ)type Ⅰ receptor (AT1R) in SHR VSMC was at significantly increased levels than in WKY VSMC.Furthermore,AngⅡ potently induced the expression of OPG in VSMC in a time- and dose-dependent manner through the AT1Rsignaling pathway.Conclusions OPG expression was substantially greater in SHR VSMC,suggesting that OPGmay be an important determinant of vascular remodeling in SHR.(J Ceriatr Cardiol 2004;1:49-54.) Osteoprotegerin (OPG) is a secreted protein of the tumor necrosis factor receptor family, which regulates bone mass by inhibiting osteoclast differentiation and activation. Although OPG is expressed ubiquitously and abundantly in many tissues and cell types including vascular cells, the role of OPG in other tissues is unknown.Our previous studies demonstrated that OPG was highly expressed in vascular smooth muscle cells (VSMC) and upregulated during vascular lesion formation. Methods and Results We documented, by Northern blot analysis, that the expression of OPG was more prevalent in the aorta and cultured VSMC from spontaneously hypertensive rats (SHR) compared to Wistar-Kyoto rats (WKY). In addition, we found that the expression of Angiotensin Ⅱ (Ang Ⅱ) type Ⅰ receptor (AT1R) in SHR VSMC was at significantly increased levels than in WKY VSMC .Furthermore, Ang II potently induced the expression of OPG in VSMC in a time- and dose-dependent manner through the AT1R signaling pathway. Conlusions O PG expression was substantially greater in SHR VSMC, suggesting that OPGmay be an important determinant of vascular remodeling in SHR. (J Ceriatr Cardiol 2004; 1: 49-54.)