Adenovirus-mediated prothymosin α gene transfer inhibits the development of atherosclerosis in apoe-deficient mice

Meng Ya Chang, Yu Shan Yang, Mei Ling Tsai, Che Hsin Lee, Chih Jui Chang, Ai Li Shiau, Chao Liang Wu

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)358-366
Number of pages9
JournalInternational Journal of Biological Sciences
Volume10
Issue number4
DOIs
Publication statusPublished - 2014 Mar 15

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this