Role of basic fibroblast growth factor and platelet-derived growth factor (B-chain) in neointima formation after arterial injury.
Balloon catheterization of rat arteries induces proliferation of smooth muscle cells (SMC) which leads to the formation of an intimal lesion. We have previously demonstrated that basic fibroblast growth factor (FGF-2) released from damaged SMC is responsible for initiating SMC proliferation, however, it is still unclear which factors are involved in the continued replication of intimal SMC. Over 95% of SMC accumulating in the intima within 8 days after balloon injury are replicating and were therefore studied as an example of a proliferating SMC, while intimal SMCs at 6 weeks after injury served as a model of quiescent SMC. When in situ hybridization for FGF-2 was carried out on en face preparations at various time points after balloon injury, increased expression of FGF-2 mRNA and protein were observed at early stages when SMC were replicating while no expression was detectable in quiescent SMCs. Strong immunoreactivity for FGF-2 was found in the cytoplasm and nucleus of proliferating SMC, whereas staining in quiescent SMC was predominantly nuclear. Platelet-derived growth factor B-chain (PDGF-B) was expressed by a subpopulation of luminal SMC during formation of the neointima. The time-course of expression for FGF-receptor 1 (FGFR-1) was similar to FGF-2 with an increase in proliferating SMC. Our data suggest that the FGF-2/FGFR-1 system may play a role in the continued proliferation of intimal SMCs, while PDGF-B may be promoting intimal lesion formation by stimulating SMC migration via its chemotactic effect.
Lindner
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University of Washington, Department of Pathology, Seattle 98195-7335, USA.
D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D003331:Coronary Vessels / Q000293:injuries* / Q000473:pathology; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D005352:Fibromuscular Dysplasia / Q000235:genetics*; D015870:Gene Expression / Q000502:physiology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017539:Tunica Intima / Q000473:pathology
D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2