Regulation of Arterial Smooth Muscle Cell Proliferation in the Intima in Patients with Occlusion of Circle of Willis (Moyamoya Disease).

我们分别从烟雾病患者和对照组的动脉中提取了5株平滑肌细胞。动脉标本取自颞浅动脉分支。研究了这些细胞的生物学特性和对生长因子的反应，并与对照组进行了比较。烟雾菌菌株和对照组在体外的寿命都有限。正常种群倍增水平（PDL）的寿命无差异。烟雾病患者的SMC在添加15%血清的培养基中增殖较对照组SMC少，对添加5%血清的PDGF反应较差。单独的PDGF在没有除牛血清白蛋白以外的血清因子的情况下，不能刺激静止状态下的SMC来启动moyainoya病的DNA合成，尽管它能显著刺激对照组。同时添加EGF、IGF-1和PDGF刺激烟雾病细胞中DNA合成的启动，但不如单独添加PDGF在对照组中的作用大。使用^<125>-I PDGF-BB进行的受体测定显示，烟雾病SMC中每个细胞的受体数量低于对照组。烟雾与对照的表观解离常数无显著差异。尽管烟雾病和对照组在每个受体中对^<125>-1 PDGF的处理没有差异，但当暴露于37 C的低浓度PDGF时，烟雾病SMC的PDGF受体在与^<125>-1 PDGF结合之前高度下调。这些结果表明细胞对PDGF反应的调节发生了改变，并且可能表明受损血管壁的修复延迟，导致烟雾病患者动脉内膜增殖速度较慢，但在某种程度上较长期。

We have established each of five strains of smooth muscle cells derived fi-om arteries of patients with moyamoya and the control. The arterial specimens were obtained from branches of superficial temporal arteries. Biological natures and the response to growth factors of these cells were examined and compared with those of the controls. Both of the strains fi-om moyamoya and the controls have a limited life span in vitro. No difference was observed in the longevity of fmal population doubling levels(PDL). SMC from patients with moyamoya disease proliferated less in a medium supplemented with 15% serum than did control SMC and responded poorly to the addition of PDGF to 5% serum. PDGF alone did not stimulate SMC in a quiescent state to initiate DNA synthesis in moyainoya disease, without serum factors other than bovine serum albumin, though it significantly stimulated the controls. Simultaneous additions of EGF, IGF-1, and PDGF stimulated initiation of DNA synthesis in cells from moyamoya disease, but not as much as PDGF alone did in the controls. Receptor assay using ^<125>-I PDGF-BB demonstrated lower receptor number per cells in SMC of moyamoya than in controls. Apparent dissociation constant was not different between moyamoya and the controls. Although processing of ^<125>-1 PDGF in each receptor was not different between moyamoya and the controls, the PDGF receptor of moyamoya SMC was highly downregulated when exposed to low concentrations of PDGF at 37ﾟC, prior to binding to ^<125>-I PDGF. These results indicate altered regulations in cellular responses to PDGF, and may indicate a delayed repair of the injured vascular wall, resulting in a slower, but somewhat longer-terin rate of intimal proliferation in arteries of patients with moyamoya disease.