Saltis J, Agrotis A, Bobik A
Baker Medical Research Institute, Alfred Hospital, Prahran, Victoria, Australia.
J Hypertens. 1993 Jun;11(6):629-37. doi: 10.1097/00004872-199306000-00007.
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.
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.
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.
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.
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.
研究自发性高血压大鼠（SHR）与正常血压的Wistar-Kyoto（WKY）大鼠血管平滑肌细胞（VSMC）生长特性的差异是否取决于生长因子的类型和性质。
在不同生长因子存在的情况下，比较SHR和WKY大鼠VSMC的生长特性。这些与VSMC上生长因子受体的表达有关。
在暴露于表皮生长因子（EGF）、碱性成纤维细胞生长因子（bFGF）或血小板衍生生长因子的三种同工型（PDGF-AA、PDGF-AB和PDGF-BB）后，检测SHR和WKY大鼠VSMC的生长速率、VSMC进入静止状态时的细胞密度以及[3H] - 胸腺嘧啶核苷掺入DNA的情况。还检测了这两种品系VSMC上这些生长因子的受体表达（受体结合和Northern分析）。
暴露于单个生长因子的SHR的VSMC表现出比WKY大鼠的VSMC更高的生长速率。对于EGF、bFGF、PDGF-AB和PDGF-BB，两品系VSMC在刺激[3H] - 胸腺嘧啶核苷掺入方面的敏感性没有差异。相反，SHR的VSMC对PDGF-AA的促有丝分裂作用表现出显著增加的敏感性。暴露于PDGF-BB或EGF的SHR的VSMC增殖，然后分别在比WKY大鼠的VSMC密度高约50%和200%时进入静止状态。相反，在bFGF存在的情况下，增殖的WKY大鼠的VSMC在比SHR的VSMC密度高约20%时进入静止状态。对[125I]标记的生长因子与两品系VSMC结合的Scatchard分析显示，所有生长因子的受体数量和解离常数相似。不同受体的稳态信使RNA水平也相似，无法解释SHR的VSMC生长速率的增加。
SHR和WKY大鼠VSMC培养物中引发的增殖反应的速率和幅度严重依赖于生长因子刺激的性质。
