Resveratrol regulates pathologic angiogenesis by a eukaryotic elongation factor-2 kinase-regulated pathway

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 pharmacological 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 pharmacological means. In addition, these results have uncovered a sirtuin-independent pathway by which resveratrol regulates angiogenesis.

Additional Info

  • Authors:

    Khan,A.A.; Dace,D.S.; Ryazanov,A.G.; Kelly,J.; Apte,R.S.

  • Issue: Am.J.Pathol. / pages 481-492 / volume 177
  • Published Date: 2010/7
  • More Information:

    For more information about this abstract, please contact
    This email address is being protected from spambots. You need JavaScript enabled to view it. at the Deutsche Weinakademie GmbH

Read 1368 times

Contact us

We love your feedback. Get in touch with us.

  • Tel: +32 (0)2 230 99 70
  • Email: This email address is being protected from spambots. You need JavaScript enabled to view it.

Disclaimer

The authors have taken reasonable care in ensuring the accuracy of the information herein at the time of publication and are not responsible for any errors or omissions. Read more on our disclaimer and Privacy Policy.