Endoglin is overexpressed after arterial injury and is required for transforming growth factor-beta-induced inhibition of smooth muscle cell migration

Endoglin is a homodimeric membrane glycoprotein primarily expressed on endo thelial cells. In association with transforming growth factor (TGF)-beta re ceptors I and II, it can bind TGF-beta1 and -beta3 and form a functional re ceptor complex. There is increasing evidence that endo,olm can modulate the cellular response to TGF-P, a factor implicated in vascular lesion formati on in human and experimental models. The purpose of this study was to analy ze the expression of endoglin in normal and balloon-injured porcine coronar y arteries and in normal and atherosclerotic human coronary arteries and to determine its ability to mediate the effects of TGF-beta an the migration of vascular smooth muscle cells (SMCs). In normal porcine coronary arteries , endoglin was of low abundance and was found primarily on endothelial cell s and adventitial fibroblasts, as well as on a minority of medial SMCs. On days 3, 7, and 14 after angioplasty, endoglin was present not only on endot helial cells but also on adventitial myofibroblasts and medial SMCs of porc ine coronary arteries. By day 28, few or no cells expressed endoglin. In si tu hybridization revealed that endoglin mRNA expression appeared to be high est in endothelial cells on days 3, 7, and 14 days after injury and absent thereafter. With a second balloon injury, a similar pattern of endoglin pro tein and mRNA expression was observed. In human vascular tissue: endoglin i mmunolabeling was higher in endarterectomy specimens removed from diseased coronary arteries than in normal internal mammary arteries. In vitro, antis ense oligonucleotides to endoglin decreased its expression and antagonized the TGF-beta -mediated inhibition of human and porcine SMC migration. In su mmary, upregulation of endoglin occurs during arterial repair and in establ ished atherosclerotic plaques and may be required for modulation of SMC mig ration by TGF-beta.