title: Endoglin is overexpressed after arterial injury and is required for transforming growth factor-beta-induced inhibition of smooth muscle cell migration.
abstract: Endoglin is a homodimeric membrane glycoprotein primarily expressed on endothelial cells. In association with transforming growth factor (TGF)-ss receptors I and II, it can bind TGF-beta1 and -beta3 and form a functional receptor complex. There is increasing evidence that endoglin can modulate the cellular response to TGF-beta, a factor implicated in vascular lesion formation in human and experimental models. The purpose of this study was to analyze the expression of endoglin in normal and balloon-injured porcine coronary arteries and in normal and atherosclerotic human coronary arteries and to determine its ability to mediate the effects of TGF-beta on the migration of vascular smooth muscle cells (SMCs). In normal porcine coronary arteries, endoglin was of low abundance and was found primarily on endothelial cells 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 endothelial cells but also on adventitial myofibroblasts and medial SMCs of porcine coronary arteries. By day 28, few or no cells expressed endoglin. In situ hybridization revealed that endoglin mRNA expression appeared to be highest 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 protein and mRNA expression was observed. In human vascular tissue, endoglin immunolabeling was higher in endarterectomy specimens removed from diseased coronary arteries than in normal internal mammary arteries. In vitro, antisense oligonucleotides to endoglin decreased its expression and antagonized the TGF-beta-mediated inhibition of human and porcine SMC migration. In summary, upregulation of endoglin occurs during arterial repair and in established atherosclerotic plaques and may be required for modulation of SMC migration by TGF-beta.
authors: Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors: X
authors: X
authors: Ma
authors: M
authors: M
authors: Labinaz
authors: J
authors: J
authors: Goldstein
authors: H
authors: H
authors: Miller
authors: W J
authors: WJ
authors: Keon
authors: M
authors: M
authors: Letarte
authors: E
authors: E
authors: O'Brien
mesh_terms: D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D015703:Antigens, CD; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D004691:Endarterectomy; D000071063:Endoglin; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D012313:RNA / Q000032:analysis; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D013552:Swine; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D016376:Oligonucleotides, Antisense; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; C509041:TGFB2 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D019010:Vascular Cell Adhesion Molecule-1; D012313:RNA; D066246:ErbB Receptors