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- Title
Sonic hedgehog myocardial gene therapy: tissue repair through transient reconstitution of embryonic signaling.
- Authors
Kusano, Kengo F.; Pola, Roberto; Murayama, Toshinori; Curry, Cynthia; Kawamoto, Atsuhiko; Iwakura, Atsushi; Shintani, Satoshi; Ii, Masaaki; Asai, Jun; Tkebuchava, Tengiz; Thorne, Tina; Takenaka, Hideya; Aikawa, Ryuichi; Goukassian, David; von Samson, Patrick; Hamada, Hiromichi; Young-sup Yoon; Silver, Marcy; Eaton, Elizabeth; Hong Ma
- Abstract
Sonic hedgehog (Shh) is a crucial regulator of organ development during embryogenesis. We investigated whether intramyocardial gene transfer of naked DNA encoding human Shh (phShh) could promote a favorable effect on recovery from acute and chronic myocardial ischemia in adult animals, not only by promoting neovascularization, but by broader effects, consistent with the role of this morphogen in embryogenesis. After Shh gene transfer, the hedgehog pathway was upregulated in mammalian fibroblasts and cardiomyocytes. This resulted in preservation of left ventricular function in both acute and chronic myocardial ischemia by enhanced neovascularization, and reduced fibrosis and cardiac apoptosis. Shh gene transfer also enhanced the contribution of bone marrow–derived endothelial progenitor cells to myocardial neovascularization. These data suggest that Shh gene therapy may have considerable therapeutic potential in individuals with acute and chronic myocardial ischemia by triggering expression of multiple trophic factors and engendering tissue repair in the adult heart.
- Subjects
GENE therapy; GENETIC transformation; CORONARY disease; NEOVASCULARIZATION; GENETIC engineering
- Publication
Nature Medicine, 2005, Vol 11, Issue 11, p1197
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/nm1313