Adenovirus-Mediated Prothymosin α Gene Transfer Reduces Atherosclerosis in ApoE-deficient Mice

• Main Authors: Yu-Shen Yang, 楊育珊
• Other Authors: Chao-Liang Wu
• Format: Others
• Language: en_US
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/04788727418757290776

碩士 === 國立成功大學 === 生物化學研究所 === 95 === Atherosclerosis is a multifactorial and complex pathological process. Oxidation and inflammation are two crucial events which are involved in the development of atherosclerotic lesions. Increased oxidative stress plays a key role in the development of endothelial dysfunction and atherosclerosis. Prothymosin a (ProT) is an abundantly expressed small nuclear protein. Early studies found that it is involved in proliferation of mammalian cells and has immunomodulatory functions. Recently, ProT was shown to be involved in regulating expression of the oxidative stress-protective genes, such as heme oxygenase-1 (HO-1). HO is the rate-limiting enzyme in heme breakdown to generate carbon monoxide, biliverdin, and free ferrous iron. Accumulating evidence has shown that inducible HO (HO-1) and its products function as adaptive molecules against oxidative insults. We hypothesized ProT overexpression might induce antioxidative genes and reduce atherosclerosis progression in apolipoprotein E-deficient mice. In our study, an adenoviral vector expressing ProT, designated “Ad/ProT”, was generated for gene therapy in ApoE-deficient mice. In vitro study, overexpression of ProT enhanced some antioxidative genes, such as HO-1 and SOD, and reduced H2O2-induced oxidative damage. Furthermore, ProT enhanced eNOS expression and increased NO release. In vivo, Ad/ProT was transfered in arteries by direct injection into the left ventricles of ApoE-deficient mice. After 4 weeks, we analysed lesion formation in the aortic sinus. We observed overexpression of ProT could reduce lesion process compared with the Ad/LacZ group.