Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 32, Issue 5, Pages 884-895Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/jcbfm.2012.2
Keywords
angiogenesis; endothelium; eNOS; MMPs; resveratrol; VEGF
Categories
Funding
- National Institutes of Health
- Conselho Nacional de Desenvolvimento e Pesquisa (CNPq)
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Resveratrol may be a powerful way of protecting the brain against a wide variety of stress and injury. Recently, it has been proposed that resveratrol not only reduces brain injury but also promotes recovery after stroke. But the underlying mechanisms are unclear. Here, we tested the hypothesis that resveratrol promotes angiogenesis in cerebral endothelial cells and dissected the signaling pathways involved. Treatment of cerebral endothelial cells with resveratrol promoted proliferation, migration, and tube formation in Matrigel assays. Consistent with these pro-angiogenic responses, resveratrol altered endothelial morphology resulting in cytoskeletal rearrangements of beta-catenin and VE-cadherin. These effects of resveratrol were accompanied by activation of phosphoinositide 3 kinase (PI3-K)/Akt and Mitogen-Activated Protein Kinase (MAPK)/ERK signaling pathways that led to endothelial nitric oxide synthase upregulation and increased nitric oxide (NO) levels. Subsequently, elevated NO signaling increased vascular endothelial growth factor and matrix metalloproteinase levels. Sequential blockade of these signaling steps prevented resveratrol-induced angiogenesis in cerebral endothelial cells. These findings provide a mechanistic basis for the potential use of resveratrol as a candidate therapy to promote angiogenesis and neurovascular recovery after stroke. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 884-895; doi:10.1038/jcbfm.2012.2; published online 8 February 2012
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