Wang, Xuanchun and Lockhart, Samuel M and Rathjen, Thomas and Albadawi, Hassan and Sørensen, Ditte and O'Neill, Brian T and Dwivedi, Nishant and Preil, Simone R and Beck, Hans Christian and Dunwoodie, Sally L and Watkins, Michael T and Rasmussen, Lars Melholt and Rask-Madsen, Christian (2016) Insulin Downregulates the Transcriptional Coregulator CITED2, an Inhibitor of Proangiogenic Function in Endothelial Cells. Diabetes, 65 (12). pp.3680-3690. ISSN 1939-327X (OA)
Full text not available from this repository.Abstract
In patients with atherosclerotic complications of diabetes, impaired neovascularization of ischemic tissue in the myocardium and lower limb limits the ability of these tissues to compensate for poor perfusion. We identified 10 novel insulin-regulated genes, among them Adm, Cited2 and Ctgf, which were downregulated in endothelial cells by insulin through FoxO1. CITED2, which was downregulated by insulin by up to 54%, is an important negative regulator of hypoxia-inducible factor (HIF) and impaired HIF signaling is a key mechanism underlying the impairment of angiogenesis in diabetes. Consistent with impairment of vascular insulin action, CITED2 was increased in cardiac endothelial cells from mice with diet-induced obesity and from db/db mice and was 3.8-fold higher in arterial tissue from patients with type 2 diabetes than non-diabetic controls. CITED2 knockdown promoted endothelial tube formation and endothelial cell proliferation while CITED2 overexpression impaired HIF activity in vitro After femoral artery ligation, induction of an endothelial-specific HIF target gene in hindlimb muscle was markedly upregulated in mice with endothelial cell deletion of CITED2, suggesting that CITED2 can limit HIF activity in vivo We conclude that vascular insulin resistance in type 2 diabetes contributes to the upregulation of CITED2 which impairs HIF signaling and endothelial pro-angiogenic function.
| Item Type: | Article |
|---|---|
| Additional Information: | This article is available for free from the publisher's website (click link above). |
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 30 Aug 2016 00:56 |
| Last Modified: | 17 Jan 2018 06:33 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/481 |
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