Sonic hedgehog myocardial gene therapy: tissue repair through transient reconstitution of embryonic signaling - PubMed (original) (raw)

. 2005 Nov;11(11):1197-204.

doi: 10.1038/nm1313. Epub 2005 Oct 23.

Roberto Pola, Toshinori Murayama, Cynthia Curry, Atsuhiko Kawamoto, Atsushi Iwakura, Satoshi Shintani, Masaaki Ii, Jun Asai, Tengiz Tkebuchava, Tina Thorne, Hideya Takenaka, Ryuichi Aikawa, David Goukassian, Patrick von Samson, Hiromichi Hamada, Young-sup Yoon, Marcy Silver, Elizabeth Eaton, Hong Ma, Lindsay Heyd, Marianne Kearney, William Munger, Jeffery A Porter, Raj Kishore, Douglas W Losordo

Affiliations

• PMID: 16244652
• DOI: 10.1038/nm1313

Sonic hedgehog myocardial gene therapy: tissue repair through transient reconstitution of embryonic signaling

Kengo F Kusano et al. Nat Med. 2005 Nov.

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.

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