Adenovirus-mediated prothymosin α gene transfer inhibits the development of atherosclerosis in ApoE-deficient mice.
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.
1. Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan; ; 2. Department of Medical Research, Buddhist Tzu-Chi General Hospital, Hualien, Taiwan;
Meng-Ya
MY
Chang
3. Department of Biochemistry and Molecular Biology, National Cheng Kung University Medical College, Tainan, Taiwan;
Yu-Shan
YS
Yang
4. Department of Physiology, National Cheng Kung University Medical College, Tainan, Taiwan;
Mei-Ling
ML
Tsai
5. Department of Microbiology, China Medical University Medical College, Taichung, Taiwan;
Che-Hsin
CH
Lee
6. Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien, Taiwan;
Chih-Jui
CJ
Chang
7. Department of Microbiology and Immunology, National Cheng Kung University Medical College, Tainan, Taiwan.
Ai-Li
AL
Shiau
3. Department of Biochemistry and Molecular Biology, National Cheng Kung University Medical College, Tainan, Taiwan;
Chao-Liang
CL
Wu
D000256:Adenoviridae; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics* / Q000502:physiology; D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D018014:Gene Transfer Techniques; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D008264:Macrophages / Q000502:physiology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress; D011498:Protein Precursors / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase; D013947:Thymosin / Q000031:analogs & derivatives* / Q000235:genetics
D000975:Antioxidants; D001057:Apolipoproteins E; D011498:Protein Precursors; D017382:Reactive Oxygen Species; C040782:prothymosin alpha; D009569:Nitric Oxide; D013947:Thymosin; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase
antioxidant gene expressions; atherosclerosis; gene transfer; prothymosin α.