Adenovirus-mediated heme oxygenase-1 gene transfer inhibits the development of atherosclerosis in apolipoprotein e-deficient mice

S. H. Juan, T. S. Lee, K. W. Tseng, J. Y. Liou, S. K. Shyue, K. K. Wu, L. Y. Chau

研究成果: 雜誌貢獻文章

283 引文 斯高帕斯(Scopus)

摘要

Background - Increasing evidence supports the role of heme oxygenase-1 (HO-1) in cytoprotective response and iron homeostasis. The object of this study was to investigate whether adenovirus-mediated gene transfer of HO-1 in arteries reduces iron overload and inhibits lesion formation in apolipoprotein E (apoE)-deficient mice. Methods and Results - Infection of rat aortic smooth muscle cells with adenovirus carrying the human HO-1 gene (Adv-HO-1) resulted in a high-level expression of HO-1 protein, which effectively reduced the hemin-induced iron overload in these cells. Adenovirus-mediated gene transfer in arteries in vivo was achieved by direct injection of Adv-HO-1 into the left ventricles of anesthetized animals. Transgene was expressed in the endothelium and aortic lesion of apoE-deficient mice after they had received recombinant adenovirus for 1 week and gradually decayed during the next 5 weeks. When young apoE-deficient mice (14 weeks old) received Adv-HO-1 (2.5×109 pfu) for 6 weeks, lesions that developed in the aortic root or aortic arch were significantly smaller than those in control littermates receiving empty viral vector. Furthermore, the iron deposition as well as tissue iron content was much less in aortic tissue of Adv-HO-1-treated mice. The inhibitory effect of HO-1 gene transfer on the progression of advanced lesions was also observed in older apoE-deficient mice (20 weeks old) receiving Adv-HO-1 intraventricularly. Conclusions - Overexpression of HO-1 in vascular cells facilitates iron metabolism and attenuates development of atherosclerosis in apoE-deficient mice.

原文英語
頁(從 - 到)1519-1525
頁數7
期刊Circulation
104
發行號13
出版狀態已發佈 - 九月 25 2001
對外發佈Yes

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

指紋 深入研究「Adenovirus-mediated heme oxygenase-1 gene transfer inhibits the development of atherosclerosis in apolipoprotein e-deficient mice」主題。共同形成了獨特的指紋。

  • 引用此

    Juan, S. H., Lee, T. S., Tseng, K. W., Liou, J. Y., Shyue, S. K., Wu, K. K., & Chau, L. Y. (2001). Adenovirus-mediated heme oxygenase-1 gene transfer inhibits the development of atherosclerosis in apolipoprotein e-deficient mice. Circulation, 104(13), 1519-1525.