STRESS-ACTIVATED SIGNALING PATHWAY AND GENE ANALYSIS IN VASCULAR CELLS DERIVED FROM PATIENTS WITH MOYAMOYA DISEASE

我们先前发现，烟雾患者培养的平滑肌细胞产生过量的前列腺素E_2，通过激活环氧合酶-2来响应白介素1，导致血管通透性增加。我们还发现，烟雾SMCs在白细胞介素1的刺激下，高度产生大量的血管内皮生长因子，这是一种强大的血管通透性因子和血管生成因子。烟雾平滑肌细胞p38丝裂原激活激酶的磷酸化上调和环氧合酶-2的激活，导致白介素1过量释放血管内皮生长因子和前列腺素E2。我们用cDNATIP检测了IL-1对烟雾病SMC基因表达的影响。我们还检测了烟雾病SMC中COX-2基因的启动子区域。进一步对家族性烟雾病患者进行连锁分析，以缩小匹配基因座的范围。对炎性刺激的高反应性被认为是烟雾病的一个显著特征，可导致内膜增厚和血管生成增强。

We previouly found that cultured smooth muscle cells from moyamoya patients produce excess amounts of prostaglandin E2 in response to interleukin-1 via activation of cyclooxygenase-2, leading to increase in vascular permeability. We also documented that moyamoya SMCs highly produce large amounts of vascular endothelial growth factor, a powerful vascular permeability factor as well as an angiogenic factor, by interleukin-1 stimulation. Up-regulated phosphorylation of p38 mitogen-activated kinase followed by activation of cyclooxygenase-2 in moyamoya smooth muscle cells contributed to the excess release of vascular endothelial growth factor and prostaglandin E2 by interleukin-1. We used cDNA tip to examine changes in mRNA expression of moyamoya SMC in response to IL-1. We also examined moyamoya SMC for the promotor region of COX-2 gene. Linkage analysis for familial moyamoya patients was further conducted to narrow down the matched locus. Higher responsiblity to inflammatory stimuli is considered to be a distinct feature of moyamoya smooth muscle cells, causing intimal thickening as well as an enhanced angiogenesis in moyamoya disease.