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.
| Original language | English |
|---|---|
| Pages (from-to) | 1197-1204 |
| Number of pages | 8 |
| Journal | Nature Medicine |
| Volume | 11 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 2005 Nov 1 |
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All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
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Sonic hedgehog myocardial gene therapy : Tissue repair through transient reconstitution of embryonic signaling. / 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; Yoon, Youngsup; Silver, Marcy; Eaton, Elizabeth; Ma, Hong; Heyd, Lindsay; Kearney, Marianne; Munger, William; Porter, Jeffery A.; Kishore, Raj; Losordo, Douglas W.
In: Nature Medicine, Vol. 11, No. 11, 01.11.2005, p. 1197-1204.Research output: Contribution to journal › Article
TY - JOUR
T1 - Sonic hedgehog myocardial gene therapy
T2 - Tissue repair through transient reconstitution of embryonic signaling
AU - Kusano, Kengo F.
AU - Pola, Roberto
AU - Murayama, Toshinori
AU - Curry, Cynthia
AU - Kawamoto, Atsuhiko
AU - Iwakura, Atsushi
AU - Shintani, Satoshi
AU - Ii, Masaaki
AU - Asai, Jun
AU - Tkebuchava, Tengiz
AU - Thorne, Tina
AU - Takenaka, Hideya
AU - Aikawa, Ryuichi
AU - Goukassian, David
AU - Von Samson, Patrick
AU - Hamada, Hiromichi
AU - Yoon, Youngsup
AU - Silver, Marcy
AU - Eaton, Elizabeth
AU - Ma, Hong
AU - Heyd, Lindsay
AU - Kearney, Marianne
AU - Munger, William
AU - Porter, Jeffery A.
AU - Kishore, Raj
AU - Losordo, Douglas W.
PY - 2005/11/1
Y1 - 2005/11/1
N2 - 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.
AB - 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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U2 - 10.1038/nm1313
DO - 10.1038/nm1313
M3 - Article
VL - 11
SP - 1197
EP - 1204
JO - Nature Medicine
JF - Nature Medicine
SN - 1078-8956
IS - 11
ER -