Purchase this article with an account.
A. A. Khan, D. Dace, A. G. Ryazanov, J. Kelly, R. S. Apte; Resveratrol Regulates Pathologic Angiogenesis by a Eukaryotic Elongation Factor-2 Kinase Pathway. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6383.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Abnormal angiogenesis is central to the pathophysiology of diverse disease processes including cancers, ischemic and atherosclerotic heart disease and visually debilitating eye disease. Resveratrol is a naturally occurring phytoalexin that has been demonstrated to ameliorate and decelerate the aging process as well as blunt end organ damage from obesity. These effects of resveratrol are largely mediated by members of the sirtuin family of proteins.
We demonstrate that resveratrol can inhibit pathological angiogenesis in vivo and in vitro by a sirtuin independent pathway. Resveratrol inhibits the proliferation and migration of vascular endothelial cells by activating eukaryotic elongation factor-2 kinase. The active kinase in turn phosphorylates and inactivates elongation factor-2, a key mediator of ribosomal transfer and protein translation. Functional inhibition of the kinase by gene deletion in vivo or RNA as well as pharmacologic inhibition in vitro is able to completely reverse the effects of resveratrol on blood vessel growth.
These studies have identified a novel and critical pathway that promotes aberrant vascular proliferation and one that is amenable to modulation by pharmacologic means. In addition, these results have uncovered a sirtuin independent pathway by which resveratrol regulates angiogenesis.
Resveratrol inhibits abnormal angiogenesis in vivo and in vitro by inhibiting eEF2 activity via eEF2 Kinase.
This PDF is available to Subscribers Only