Suppression of vascular remodeling via modulation of redox regulation and basic excision repair of oxidative DNA damge

在袖套致血管损伤模型中，观察了受损的还原型谷胱甘肽(GSH)氧化还原系统对血管紧张素II诱导的血管重塑的影响。丁硫氨酸亚磺胺(BSO)治疗可使GSH氧化还原功能受损，其本身并不影响血流动力学。血管紧张素II BSO可显著增加血管壁超氧化物歧化产物的生成，但氧化还原系统受损的血管重塑完全消失。我们已经阐明，这种机制是通过促进新生内膜的凋亡和抑制中膜细胞的生长来实现的。同时，我们证实了APE1基因在金属丝损伤的小鼠动脉中的表达增强，特别是在新生内膜病变中。成功构建了AP1基因插入载体，并转染腺病毒。研究AP1基因作为碱基切除修复系统在动脉粥样硬化过程中的关键作用，探讨AP1基因在过氧化氢诱导血管平滑肌细胞氧化损伤中的作用。BER系统与抗动脉粥样硬化机制的相互作用已经在体内模型中得到了研究，并被认为是防治动脉粥样硬化的新靶点。

Alteration of angiotensin II-induced vascular remodeling was investigated in impaired reduced glutathione (GSH) redox system in cuff-induced vascular injury mode. The impaired GSH redox status was set by buthionine sulfoximine (BSO) treatment, which did not affect hemodynamics by itself. Superoxide production in vascular wall was markedly enhanced in angiotensin II+BSO, however, the vascular remodeling.induced by angiotensin II was totally abolished in the impaired redox system. We have elucidated that the mechanism was actuated via enhancement of apoptosis in the neointima and suppression of cell growth in the media. Meanwhile, we have confirmed the enhanced expression of Ape1 gene in the wire-injured arteries of mice, particularly in the neointimal lesion. We have produced AP1 gene inserted plasmid and trasnfected to adenovirus. The role of AP1 gene as a key player of base excision repair (BER) system in atherosclerosis process was investigated in the H2O2-induced oxidative damage in cultured vascular smooth muscle cells. The interaction of BER system and antiatherosclerotic mechanism has been investigated in in vivo model, and has been proposed as the new target for atherosclerosis threatment.