Combined Gene Therapy with Hypoxia-Inducible Factor-1α and Heme Oxygenase-1 for Therapeutic Angiogenesis
Transfection with either hypoxia-inducible factor-1α ( HIF-1α ) or heme oxygenase-1 ( HO-1 ) gene can induce neovascularization in ischemic tissues. Although expression of transfected HIF-1α gene occurs rapidly, the expressed HIF-1α protein degrades quickly, limiting its therapeutic efficacy. Meanwh...
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Published in | Tissue engineering. Part A Vol. 17; no. 7-8; pp. 915 - 926 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Mary Ann Liebert, Inc
01.04.2011
|
Subjects | |
Online Access | Get full text |
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Summary: | Transfection with either hypoxia-inducible factor-1α (
HIF-1α
) or heme oxygenase-1 (
HO-1
) gene can induce neovascularization in ischemic tissues. Although expression of transfected
HIF-1α
gene occurs rapidly, the expressed HIF-1α protein degrades quickly, limiting its therapeutic efficacy. Meanwhile, expressed HO-1 protein does not rapidly undergo degradation, but gene expression occurs a couple of days after transfection, resulting in apoptosis and a delay in angiogenesis in ischemic tissues at the incipient period of
HO-1
gene transfection. We hypothesize that combined delivery of
HIF-1α
and
HO-1
gene will enhance antiapoptosis and neovascularization in ischemic tissue compared with
HIF-1α
or
HO-1
single-gene therapy. To test this hypothesis, ischemic mouse hindlimbs were treated with
HIF-1α
and/or
HO-1
gene therapy. The combined gene therapy proved superior to both single-gene therapies, resulting in rapid expression of
HIF-1α
gene and long-term maintenance of expressed HO-1 protein. The apoptosis in the ischemic region was significantly less, and angiogenic growth factor secretion and angiogenesis were greater in the combined gene therapy than in either of the single-gene therapies. Our results suggest that a combined gene therapy of
HIF-1α
and
HO-1
enhances the transfection of both genes and improves angiogenesis compared with either single-gene therapy. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1937-3341 1937-335X |
DOI: | 10.1089/ten.tea.2010.0493 |