Molecular Biological Analysis of Patients with Moyamoya Disease

烟雾病的主要病变是颅内动脉主干狭窄，这被认为是导致广泛的侧支循环，包括大脑底部的精细血管网络。然而，烟雾病的病因仍然不明，病理生理机制仍然没有得到证实。碱性成纤维细胞生长因子（BFGF）是一种有效的促有丝分裂剂，用于多种细胞类型，包括血管内皮细胞和平滑肌细胞。为了检测BFGF参与烟雾病内膜增厚发病机制的可能性，我们使用小鼠抗人BFGF单克隆抗体检测BFGF的存在。我们用化学方法证明烟雾病患者颞浅动脉（STA）中bFGF的含量增加。然后，我们进行了STA的免疫组织化学研究，使用多克隆抗人FGF受体（FLG）抗体，以阐明BFGF的功能。本研究表明，在平滑肌细胞中，bFGF与bFGF受体共存。因此，我们推测，富含BFGF的平滑肌细胞可能通过自分泌机制刺激自身，并迁移到内膜中，然后将其重新定位。虽然我们进行了DNA印迹分析，以检查BFGF和BFGF受体基因的变化，我们不能发现烟雾病患者的BFGF和BFGF受体基因的主要变化。此外，我们进行了聚合酶链反应（PCR）检测单纯疱疹病毒（HSV）基因组在烟雾病患者。然而，HSV基因组在正常成人和烟雾病患者中都以高频率存在。我们未能阐明BFGF产量增加的原因。需要进一步检查以揭示BFGF产量增加的原因。

The primary lesion of moyamoya disease is stenosis of the intracanial arterial trunk, which is thought to result in extensive collateral circulation, including a fine network of vessels at the base of the brain. However, the cause of moyamoya disease remains unknown, and pathophysiological mechanisms remain unproven. Basic fibroblast growth factor (BFGF) is a potent mitogen for a number of cell types including vascular endothelial and smooth muscle cells. In order to test the possibility that BFGF takes part in the pathogenesis of the intimal thickening of moyamoya disease, we tested for the presence of BFGF using a mouse anti-human BFGF monoclonal antibody. We demonstrated immunohistochemically that the amount of BFGF is increased in the superficial temporal artery (STA) of patients with moyamoya disease. Then, we performed an immunohistochemical study of STA using a polyclonal anti-human FGF receptor (FLG) antibody to clarify the function of BFGF. This study demonstrated that BFGF coexists with BFGF receptor in smooth muscle cells. Thus, we speculate that smooth muscle cells with abundant BFGF may stimulate themselves through an autocrine mechanism and migrate into the intima and then thicken it. Although we performed DNA blot analyses to examine a change in the BFGF and BFGF receptor gene, we could not find out the major change in the BFGF and BFGF receptor gene of patients with moyamoya disease. In addition, we have performed polymerase chain reaction (PCR) to detect herpes simplex virus (HSV) genomes in patients with moyamoya disease. However, HSV genomes are present in both normal adults and patients with moyamoya disease in a high frequency. We have failed to elucidate the cause of the increased production of BFGF. Further examination is required to reveal the cause of the increased production of BFGF.