The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals

Yasuko Kureishi, Zhengyu Luo, Ichiro Shiojima, Ann Bialik, David J Fulton, David J. Lefer, William C. Sessa, Kenneth Walsh

Research output: Contribution to journalArticle

1217 Citations (Scopus)

Abstract

Recent studies suggest that statins can function to protect the vasculature in a manner that is independent of their lipid-lowering activity. We show here that statins rapidly activate the protein kinase Akt/PKB in endothelial cells. Accordingly, simvastatin enhanced phosphorylation of the endogenous Akt substrate endothelial nitric oxide synthase (eNOS), inhibited apoptosis and accelerated vascular structure formation in vitro in an Akt-dependent manner. Similar to vascular endothelial growth factor (VEGF) treatment, both simvastatin administration and enhanced Akt signaling in the endothelium promoted angiogenesis in ischemic limbs of normocholesterolemic rabbits. Therefore, activation of Akt represents a mechanism that can account for some of the beneficial side effects of statins, including the promotion of new blood vessel growth.

Original languageEnglish (US)
Pages (from-to)1004-1010
Number of pages7
JournalNature Medicine
Volume6
Issue number9
DOIs
StatePublished - Sep 1 2000
Externally publishedYes

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Simvastatin
Protein Kinases
Animals
Blood Vessels
Phosphorylation
Nitric Oxide Synthase Type III
Endothelial cells
Blood vessels
Vascular Endothelial Growth Factor A
Endothelium
Extremities
Endothelial Cells
Chemical activation
Apoptosis
Rabbits
Lipids
Substrates
Growth

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. / Kureishi, Yasuko; Luo, Zhengyu; Shiojima, Ichiro; Bialik, Ann; Fulton, David J; Lefer, David J.; Sessa, William C.; Walsh, Kenneth.

In: Nature Medicine, Vol. 6, No. 9, 01.09.2000, p. 1004-1010.

Research output: Contribution to journalArticle

Kureishi, Yasuko ; Luo, Zhengyu ; Shiojima, Ichiro ; Bialik, Ann ; Fulton, David J ; Lefer, David J. ; Sessa, William C. ; Walsh, Kenneth. / The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. In: Nature Medicine. 2000 ; Vol. 6, No. 9. pp. 1004-1010.
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