© 1997 American Heart Association, Inc.
Articles |
Inducible Expression of Egr-1–Dependent Genes
A Paradigm of Transcriptional Activation in Vascular Endothelium
From The Centre for Thrombosis and Vascular Research (L.M.K.), School of Pathology, The University of New South Wales, Sydney, Australia, and the Vascular Research Division (T.C.), Brigham and Women's Hospital and Harvard Medical School, Boston, Mass.
Correspondence to Levon M. Khachigian, PhD, The Centre for Thrombosis and Vascular Research, School of Pathology, The University of New South Wales, Sydney NSW 2052, Australia. E-mail L.Khachigian@unsw.edu.au
Key Words: early growth response factor-1 • platelet-derived growth factor • transcription
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Introduction |
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Throughout the vascular network, endothelium forms the continuous cellular interface between the circulating blood elements and the surrounding tissues. These cells provide a nonthrombogenic surface and a permeability barrier capable of modulating blood flow and vascular reactivity. As such, the integrity of the endothelium is a fundamental requirement for the maintenance of normal homeostasis. Injury to this lining and the subsequent inflammatory response are among the earliest cellular events in the pathogenesis of atherosclerosis.1 This can result in dramatic phenotypic changes that render otherwise quiescent endothelium adhesive and prothrombotic. Lesions of atherosclerosis and postangioplasty restenosis may develop under the influence of molecules inducibly expressed or simply released by activated or injured endothelium. Several lines of evidence over the last decade, based on ligand and receptor localization, overexpression, and infusion studies, have correlated PDGF with the development of vascular occlusive lesions. PDGF appears to play a regulatory role in the migratory, rather than proliferative, events associated with the response to arterial injury. PDGF expression is quite low in the quiescent vessel wall, but levels of the growth factor increase substantially after injury. This Mini Review will focus on the transcriptional mechanisms underlying inducible PDGF expression in vascular endothelium and smooth muscle cells, with particular emphasis on the role played by the early growth response gene product, Egr-1.
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Sp1 Mediates Basal PDGF Gene Expression |
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The vessel wall responds to a changing local environment by modulating the expression of specific sets of genes. Transcriptional activation in response to these signals involves the regulated assembly of multiprotein complexes on promoters.
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