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

在袖带诱导的血管损伤模型中，研究了还原型谷胱甘肽（GSH）氧化还原系统受损对血管紧张素II诱导的血管重构的影响。受损的GSH氧化还原状态是由丁硫基乙砜亚胺（BSO）治疗，这本身并不影响血流动力学。血管紧张素Ⅱ +BSO可明显促进血管壁超氧化物的产生，而氧化还原系统受损则可完全消除血管紧张素Ⅱ诱导的血管重构。我们已经阐明了其机制是通过促进新生内膜中的凋亡和抑制中膜中的细胞生长来驱动的。同时，我们证实了Ape1基因在小鼠动脉丝损伤后的表达增强，特别是在新生内膜病变中。我们制备了AP 1基因插入质粒，并将其转染到腺病毒中。本研究以H_2O_2诱导的血管平滑肌细胞氧化损伤为模型，探讨了AP 1基因作为动脉粥样硬化过程中碱基切除修复（BER）系统的关键参与者的作用。BER系统与抗动脉粥样硬化机制的相互作用已在体内模型中得到研究，并被认为是治疗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.