FUNCTIONAL ALTERATIONS IN VASCULAR CELLS OF PATIENTS WITH MOYAMOYA DISEASE.

在烟雾病中，由于纤维细胞内膜增厚导致的双侧颈内动脉进行性狭窄或闭塞导致脑缺血。我们最近发现，烟雾病患者动脉来源的培养的平滑肌细胞(SMC)对血清有丝分裂原反应很差，尤其是对血小板衍生生长因子(PDGF)。在本研究中，我们进一步研究了烟雾病患者动脉SMC中β-PDGF的结合和加工，以及PDGF受体的下调。烟雾病患者血管内皮细胞表面4ﾟC和22ﾟC处的β-lt；125&gt；i-PDGF的特异性结合位点数均显著低于对照组，而表观解离常数(Kd)无明显变化。烟雾病患者细胞在37ﾟC时的结合动力学表明，与对照组相比，结合部位较少，细胞内降解率较低，但各受体的内化或降解率无明显差异。37ﾟC的低浓度非标记血小板衍生生长因子作用下，烟雾病患者细胞表面剩余结合位点数明显低于对照组。烟雾病SMC中PDGF受体的过度下调可能被解释为PDGF受体循环不足或细胞内池减少。这些结果与烟雾病SMC对PDGF的增殖反应减弱密切相关，为血管细胞功能改变参与了烟雾病内膜增厚的发生机制提供了证据。

Progressive stenosis or occlusion of bilateral internal carotid arteries by fibrocellular intimal thickening results in cerebral ischemia in moyamoya disease. We recently found that cultured smooth muscle cells (SMC) derived from arteries of patients with moyamoya disease responded poorly to serum mitogens, especially to platelet-derived growth factor (PDGF). In the present study, we investigated further the binding and processing of ^<125>I-PDGF, as well as down-regulation of the PDGF receptor in arterial SMC derived from patients with moyamoya disease. The specific binding sites of ^<125>I-PDGF were reduced significantly at both 4ﾟC and 22ﾟC on SMC from moyamoya disease compared with those from controls, though the apparent dissociation constant (Kd) were the same. Kinetics of ^<125>I-PDGF binding at 37ﾟC in cells from moyamoya disease showed fewer binding site and lower degradation per cell than in those from controls, though no difference was observed in either internalization or degradation of each receptor. When SMC were exposed to lower concentrations of nonlabeled PDGF at 37ﾟC, the percentage of remaining binding site on cells from moyamoya disease was significantly less than that from controls. This excess down-regulation of PDGF receptor in SMC from moyamoya disease may be interpreted as insufficient recycling or a decreased intracellular pool of the PDGF receptor. These results are closely correlated with the diminished proliferation responses to PDGF in SMC from moyamoya disease and provide evidence that functional alterrations in vascular cells are involved in the mechanism of development of intimal thickening in moyamoya disease.