(Circulation. 1997;95:555-556.)
© 1997 American Heart Association, Inc.
Articles |
Platelet-Derived Growth Factor and Arterial Response to Injury
ZymoGenetics, Inc, Seattle, Wash (C.E.H.), and the University of Washington School of Medicine, Seattle.
Correspondence to Alexander W. Clowes, MD, Department of Surgery, University of Washington School of Medicine, HSB 442, Box 356410, Seattle, WA 98195.
Key Words: Editorials • arteries • platelet-derived factors • receptors
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Introduction |
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Platelet-derived growth factor (PDGF) was identified as the first human homologue of a retroviral transforming gene (c-sis).1 2 Since that initial discovery, the complexity of the PDGF system has continued to be unraveled. PDGF is a family of proteins comprising two separate gene products, PDGF-A and PDGF-B chains.3 The individual proteins are able to form the covalent dimers AA, AB, and BB. In addition to the three isoforms of PDGF, there are two receptor polypeptides called
and ß. The PDGF- receptor is able to bind both the PDGF-A and PDGF-B chains, whereas the PDGF-ß receptor binds only the PDGF-B chain. In the presence of ligand, the receptors form dimers on the cell surface so that / dimers bind all three PDGF isoforms (AA, AB, and BB), /ß dimers bind AB and BB, and ß/ß dimers bind only PDGF-BB.4 The specificity provided by the receptors dictates to which type of PDGF a cell is able to respond.
Although PDGF was initially isolated from platelets, it has also been shown to be expressed by all vascular wall cells, including smooth muscle cells (SMCs), endothelial cells, and macrophages. When rats are made thrombocytopenic or are treated with a polyclonal antibody to all forms of PDGF, intimal thickening induced by balloon catheter injury is inhibited even though the first wave of proliferation in the media is not blocked.5 6 Polyclonal antibodies specific for the PDGF-B chain also are able to block intimal thickening, whereas antibodies specific for the PDGF-A chain have no effect on
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