Vascular endothelial function and blood pressure homeostasis in mice overexpressing IGF binding protein-1.
IGFs and their binding proteins (IGFBPs) play a significant role in metabolic regulation, and there is growing evidence that they also exert important vascular effects. IGFBP-1 contributes to glucose counterregulation, and observational studies demonstrate an inverse association between circulating IGFBP-1 levels and cardiovascular risk factors. Furthermore, IGFBP-1 levels are lower in subjects with overt macrovascular disease. We therefore hypothesized that IGFBP-1 exerts potentially beneficial effects, either directly or indirectly, on blood pressure regulation and vascular function. We tested this hypothesis using a unique transgenic mouse, which overexpresses human IGFBP-1, and explored the effect of this protein on metabolic, blood pressure, and vascular homeostasis. IGFBP-1-overexpressing mice exhibited postprandial hyperinsulinemia with preservation of glucocompetence and insulin sensitivity. Blood pressure was unchanged in the fasting state but was significantly lower in transgenic mice after a carbohydrate load. Aortic rings from IGFBP-1-overexpressing mice were hypocontractile in response to vasoconstrictors, and relaxation responses were unimpaired. Basal nitric oxide production was increased and endothelial nitric oxide synthase mRNA expression upregulated in aortae of these mice. Our data suggest that IGFBP-1 plays an important and potentially beneficial role in regulating metabolic and vascular homeostasis.
Wheatcroft
Stephen B
SB
Department of Cardiology, Guy's, King's and St. Thomas' School of Medicine, London, UK.
Kearney
Mark T
MT
Shah
Ajay M
AM
Grieve
David J
DJ
Williams
Ian L
IL
Miell
John P
JP
Crossey
Paul A
PA
D000818:Animals; D001011:Aorta / Q000502:physiology*; D001794:Blood Pressure / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000502:physiology*; D015870:Gene Expression; D006706:Homeostasis / Q000502:physiology; D007328:Insulin / Q000378:metabolism; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D012307:Risk Factors; D014661:Vasoconstriction / Q000502:physiology
D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D008055:Lipids; D007334:Insulin-Like Growth Factor I; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse