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

Autor: Ryuichi Aikawa, Hideya Takenaka, Hiromichi Hamada, Marianne Kearney, David A. Goukassian, Young Sup Yoon, Jeffery A. Porter, Elizabeth Eaton, Satoshi Shintani, Tengiz Tkebuchava, Masaaki, Lindsay Heyd, Raj Kishore, Tina Thorne, Jun Asai, William E. Munger, Hong Ma, Atsuhiko Kawamoto, Douglas W. Losordo, Cynthia Curry, Atsushi Iwakura, Kengo Fukushima Kusano, Roberto Pola, Patrick von Samson, Marcy Silver, Toshinori Murayama
Rok vydání: 2005
Předmět:
Swine
Genetic enhancement
Myocardial Ischemia
Ventricular Function
Left
Neovascularization
Mice
Chlorocebus aethiops
Myocytes
Cardiac
Sonic hedgehog
Cells
Cultured
Regulation of gene expression
biology
Reverse Transcriptase Polymerase Chain Reaction
Gene Expression Regulation
Developmental
Heart
General Medicine
gene therapy
Hedgehog signaling pathway
Cell biology
Naked DNA
Echocardiography
embryonic structures
Acute Disease
COS Cells
medicine.symptom
Morphogen
Signal Transduction
medicine.medical_specialty
animal structures
Neovascularization
Physiologic
General Biochemistry
Genetics and Molecular Biology
sonic hedgehog
Internal medicine
medicine
Animals
Humans
Hedgehog Proteins
RNA
Messenger
Progenitor cell
Myocardium
Settore MED/09 - MEDICINA INTERNA
Genetic Therapy
Fibroblasts
Mice
Mutant Strains
Rats
Disease Models
Animal
Endocrinology
Chronic Disease
biology.protein
Trans-Activators
Zdroj: Nature medicine. 11(11)
ISSN: 1078-8956
Popis: 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.
Databáze: OpenAIRE
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