SIRT1 controls endothelial angiogenic functions during vascular growth.

By M. Potente, L. Ghaeni, D. Baldessari, R. Mostoslavsky, L. Rossig, F. Dequiedt, J. Haendeler, M. Mione, E. Dejana, F. Alt and 2 more. Genes & Development, 2007

635 citations recorded by the source corpus.

The nicotinamide adenine dinucleotide (NAD(+))-dependent histone deacetylase Sir2 regulates life-span in various species. Mammalian homologs of Sir2 are called sirtuins (SIRT1-SIRT7). In an effort to define the role of sirtuins in vascular homeostasis, we found that among the SIRT family, SIRT1 uniquely regulates angiogenesis signaling. We show that SIRT1 is highly expressed in the vasculature during blood vessel growth, where it controls the angiogenic activity of endothelial cells. Loss of SIRT1 function blocks sprouting angiogenesis and branching morphogenesis of endothelial cells with consequent down-regulation of genes involved in blood vessel development and vascular remodeling. Disruption of SIRT1 gene expression in zebrafish and mice results in defective blood vessel formation and blunts ischemia-induced neovascularization. Through gain- and loss-of-function approaches, we show that SIRT1 associates with and deacetylates the forkhead transcription factor Foxo1, an essential negative regulator of blood vessel development to restrain its anti-angiogenic activity. These findings uncover a novel and unexpected role for SIRT1 as a critical modulator of endothelial gene expression governing postnatal vascular growth.

Subfields: Cancer Research, Geriatrics and Gerontology, Physiology

View Paper: https://www.semanticscholar.org/paper/34d1052d1ebfb9b121844087588a759c7811ccba

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In Geriatrics and Gerontology

1. V. Sartorelli
2. Eric P. Hoffman
3. Yana Cen
4. M. Fulco
5. Po Zhao
6. A. Sauve
7. M. McBurney

In Physiology

1. A. Sauve
2. M. McBurney

Citations in the corpus

• Glucose restriction inhibits skeletal myoblast differentiation by activating SIRT1 through AMPK-mediated regulation of Nampt. (2008, background): “Differentiation of skeletal muscle cells (Fulco et al., 2003) and adipocytes (Picard et al., 2004), angiogenesis (Potente et al., 2007), survival of neurons (Araki et al., 2004) and pancreatic β-cells (Kitamura et al., 2005), insulin secretion (Bordone et al., 2006) (Moynihan et al., 2005), lipid…”