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- Title
Novel Role of the IGF-1 Receptor in Endothelial Function and Repair.
- Authors
Imrie, Helen; Viswambharan, Hema; Sukumar, Piruthivi; Abbas, Afroze; Cubbon, Richard M.; Yuldasheva, Nadira; Gage, Matthew; Smith, Jessica; Galloway, Stacey; Skromna, Anna; Rashid, Sheik Taqweer; Futers, T. Simon; Xuan, Shouhong; Gatenby, V. Kate; Grant, Peter J.; Channon, Keith M.; Beech, David J.; Wheatcroft, Stephen B.; Kearney, Mark T.
- Abstract
We recently demonstrated that reducing IGF-1 receptor (IGF-1R) numbers in the endothelium enhances nitric oxide (NO) bioavailability and endothelial cell insulin sensitivity. In the present report, we aimed to examine the effect of increasing IGF-1R on endothelial cell function and repair. To examine the effect of increasing IGF-1R in the endothelium, we generated mice overexpressing human IGF-1R in the endothelium (human IGF-1R endothelium-overexpressing mice [hIGFREO]) under direction of the Tie2 promoter enhancer. hIGFREO aorta had reduced basal NO bioavailability (percent constriction to NG-monomethyl-Larginine [mean (SEM) wild type 106% (30%); hIGFREO 48% (10%)]; P , 0.05). Endothelial cells from hIGFREO had reduced insulin-stimulated endothelial NO synthase activation (mean [SEM] wild type 170% [25%], hIGFREO 58% [3%]; P = 0.04) and insulin-stimulated NO release (mean [SEM] wild type 4,500 AU [1,000], hIGFREO 1,500 AU [700]; P , 0.05). hIGFREO mice had enhanced endothelium regeneration after denuding arterial injury (mean [SEM] percent recovered area, wild type 57% [2%], hIGFREO 47% [5%]; P , 0.05) and enhanced endothelial cell migration in vitro. The IGF-1R, although reducing NO bioavailability, enhances in situ endothelium regeneration. Manipulating IGF-1R in the endothelium may be a useful strategy to treat disorders of vascular growth and repair.
- Subjects
INSULIN-like growth factor receptors; ENDOTHELIUM; NITRIC oxide; BIOAVAILABILITY; ENDOTHELIAL cells
- Publication
Diabetes, 2012, Vol 61, Issue 9, p2359
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db11-1494