1. Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan;
2. Department of Medical Research, Buddhist Tzu-Chi General Hospital, Hualien, Taiwan;
3. Department of Biochemistry and Molecular Biology, National Cheng Kung University Medical College, Tainan, Taiwan;
4. Department of Physiology, National Cheng Kung University Medical College, Tainan, Taiwan;
5. Department of Microbiology, China Medical University Medical College, Taichung, Taiwan;
6. Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien, Taiwan;
7. Department of Microbiology and Immunology, National Cheng Kung University Medical College, Tainan, Taiwan.
Prothymosin α (ProT) is involved in regulating expression of the oxidative stress-protective genes and it also exerts immunomodulatory activities. In this study, we investigated the therapeutic effects of ProT gene transfer on atherosclerosis in endothelial cells and in ApoE-deficient mice. Adenoviruses encoding mouse ProT (AdProT) were used for the management of atherosclerosis. In vitro, the effects of ProT on antioxidant gene expressions and the protection effect against oxidant-mediated injury in endothelial cells were examined. In vivo, AdProT were administered intraventricularly into the heart of ApoE-/- mice. Histopathological and immunohistochemical assessments of the aortic tissues were performed. Expressions of HO-1 and antioxidant genes in the aortic tissues were also determined. Our results demonstrated that ProT gene transfer increased antioxidant gene expressions, eNOS expression and NO release, as well as reduced the reactive oxygen species production in endothelial cells. Intraventricular administration of AdProT reduced the lesion formation, increased expressions of HO-1 and SOD genes, and reduced infiltrating macrophages in the aorta of ApoE-/- mice. This study suggests that ProT gene transfer may have the therapeutic potential for the management of atherosclerosis via inducing antioxidant gene expressions, eNOS expression and NO release, reducing ROS production and macrophage infiltration in endothelium.
Keywords: atherosclerosis, gene transfer, antioxidant gene expressions, prothymosin α.