Novel Role of the IGF-1 Receptor in Endothelial Function and Repair: Studies in Endothelium-Targeted IGF-1 Receptor Transgenic Mice

作者：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^*

来源：Diabetes, 2012, 61(9): 2359-2368.

DOI：10.2337/db11-1494

We recently demonstrated that reducing IGF-1 receptor (IGF-1R) numbers in the endothelium enhances nitric oxide (NO) bio-availability 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 over-expressing 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 N-G-monomethyl-L-arginine [mean (SEM) wild type 106% (30%); hIGFREO 48% (10%)]; P %26lt; 0.05). Endothelial cells from hIGFREO had reduced insulin-stimulated endothelial NO synthase activation (mean [SEMI wild type 170% [25%], hIGFREO 58% [3%]; P = 0.04) and insulin-stimulated NO release (mean [SEMI wild type 4,500 AU [1,000], hIGFREO 1,500 AU [700]; P %26lt; 0.05). hIGFREO mice had enhanced endothelium regeneration after denuding arterial injury (mean [SEMI percent recovered area, wild type 57% [2%], hIGFREO 47% [5%]; P %26lt; 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. Diabetes 61:2359-2368, 2012

• 出版日期2012-9