Differences in growth characteristics of vascular smooth muscle from spontaneously hypertensive and Wistar???Kyoto rats are growth factor dependent

OBJECTIVE: To investigate whether the differences in the growth properties between vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats depend on the type and nature of the growth factor. DESIGN: The growth characteristics of VSMC from SHR and WKY rats were compared in the presence of different growth factors. These were related to growth factor receptor expression on the VSMC. METHODS: Growth rates, cell densities at which VSMC become quiescent and [3H]-thymidine incorporation into DNA were examined in VSMC from SHR and WKY rats following exposure to epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) or the three isoforms of platelet-derived growth factor (PDGF-AA, PDGF-AB and PDGF-BB). Receptor expression (receptor binding and Northern analysis) for these growth factors was also examined on VSMC from the two strains. RESULTS: VSMC from SHR exposed to the individual growth factors exhibited growth rates higher than those from WKY rats. For EGF, bFGF, PDGF-AB and PDGF-BB there was no difference in the sensitivity of VSMC to stimulation of [3H]-thymidine incorporation between the strains. In contrast, VSMC from SHR exhibited significantly increased sensitivity to the mitogenic effects of PDGF-AA. VSMC from SHR exposed to PDGF-BB or EGF proliferated and then became quiescent at densities approximately 50 and 200% higher, respectively, than those from WKY rats. In contrast, in the presence of bFGF, proliferating VSMC from WKY rats became quiescent at densities approximately 20% higher than those from SHR. Scatchard analysis of [125I]-labelled growth factor binding to VSMC from the two strains revealed similar receptor numbers and dissociation constants for all growth factors. Steady-state messenger RNA levels for the different receptors were also similar and could not account for the enhanced growth rates of VSMC from SHR. CONCLUSION: The rate and magnitude of the proliferative response elicited in VSMC cultures from SHR and WKY rats is critically dependent on the nature of the growth factor stimulus.