STRESS-ACTIVATED SIGNALING IN VASCULAR SMOOTH MUSCLE CELLS DERIVED FROM PATIENTS WITH MOYAMOYA DISEASE

烟雾病是一种主要影响儿童的进行性脑血管闭塞性疾病。主要的血管病灶狭窄或闭塞，伴有内膜纤维细胞增厚。事故原因尚不清楚。我们之前发现，烟雾病患者培养的平滑肌细胞通过激活环氧化酶-2，对白细胞介素-1产生过量的前列腺素E2，导致血管通透性增加。在这里，我们证明了烟雾SMCs通过白细胞介素-1刺激大量产生血管内皮生长因子，这是一种强大的血管通透性因子和血管生成因子。烟雾平滑肌细胞中p38丝裂原活化激酶磷酸化上调，随后环氧化酶-2激活，导致白细胞介素-1过量释放血管内皮生长因子和前列腺素E2。对炎症刺激的更高责任是烟雾平滑肌细胞的一个明显特征，引起内膜增厚以及通过p38丝裂原激活的激酶磷酸化机制紊乱而增强的血管生成。

Moyamoya disease is a progressive cerebrovascular occlusive disease affecting primarily children. The main vascular leions are stenosis or occlusion with fibrocellular thickening of the intima. The cause remains unknown. 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. Here, we demonstrate 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. Higher responsibility to inflammatory stimuli is a distinct feature of moyamoya smooth muscle cells, causing intimal thickening as well as an enhanced angiogenesis via disordered p38 mitogen-activated kinase phosphorylation machinery.