Insulin-like growth factor I plasmid therapy promotes in vivo angiogenesis

82Citations
Citations of this article
47Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Angiogenesis, the formation of neovessels from the endothelium of preexisting vessels, is stimulated by soluble angiogenic factors. Insulin-like growth factor I (IGF-I) stimulates myogenesis and induces nerve regeneration after injury, and it has been shown to stimulate angiogenesis. However, the in vivo angiogenic effects of IGF-I in regenerating and diabetic muscle have yet to be described. Therefore, we studied the effects of human IGF-I (hIGF-I) delivered by a plasmid-mediated therapy on angiogenesis in mouse models of these two conditions. Plasmid hIGF-I was delivered to the injured tibialis muscle by direct intramuscular injection followed by electroporation. Initial experiments compared two muscle-specific hIGF-I-expressing constructs containing either a skeletal actin 3′UTR (pAV2001) or a human growth hormone (GH) 3′UTR (pAV2002). Skeletal actin 3′UTR mediates sequestration of hIGF-I in the muscle and was more active, while the GH 3′UTR mediated release of IGF-I into the circulation. Treatment of regenerating muscle with pAV2001 and sequestration of IGF-I in muscle led to increased expression of vascular endothelial growth factor (VEGF) and VEGF receptors fetal liver kinase-1 and FmS-like tyrosine kinase receptor-1, as well as platelet endothelial cell adhesion molecule-1, on endothelial cells. These results indicate that IGF-I can amplify angiogenic responses in regenerating muscle. In a mouse diabetic model, plasmid-mediated IGF-I therapy reversed diabetic microangiopathy, as shown by increased angiogenesis and arterial flow as analyzed by Doppler imaging. These studies show that plasmid IGF-I delivery and sequestration in muscle can augment angiogenesis in regenerating muscle and increase blood flow and angiogenesis in the diabetic limb.

Cite

CITATION STYLE

APA

Rabinovsky, E. D., & Draghia-Akli, R. (2004). Insulin-like growth factor I plasmid therapy promotes in vivo angiogenesis. Molecular Therapy, 9(1), 46–55. https://doi.org/10.1016/j.ymthe.2003.10.003

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free