The Role of Platelet-Derived Growth Factor in AtherogenesisPlatelet-derived growth factor (PDGF) may be responsible for the intimal smooth muscle cell proliferation of atherosclerosis. 9 This concept originated from the observation that platelets contain a potent mitogen for smooth muscle cells, PDGF, and that platelets accumulate and degranulate at sites of endothelial disruption. Although PDGF remains of great interest, it is now apparent that many cells produce PDGF: macrophage, endothelial, and smooth muscle cells (at least in vitro).
Therefore, although the platelet may be important in early PDGF release, it now seems likely that endogenous PDGF may be of greater long-term importance. In 1991, Ross demonstrated that antibodies to PDGF prevented the myointimal proliferation observed following balloon angioplasty, raising the question, "Could this have important implications for smooth muscle cells in atherosclerotic plaques?" These PDGF-producing cells also occur in human atherosclerotic plaque. PDGF gene expression has now been clearly demonstrated within human carotid plaque (probably smooth muscle).
PDGF -chain and -chain messenger RNAs can be localized to mesenchymal-appearing intimal cells within the intima. PDGF receptor probes also localize to the intima. Smooth muscle cells (SMCs) in the media do not elaborate PDGF or receptor mRNA. Consequently, the PDGF hypothesis has been changed so that endogenous production of PDGF, locally produced within the plaque, may play an important role in smooth muscle cell proliferation.
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