University of Louisville
Role of Caveolae in Cardioprotective Activity of the Red Wine Polyphenol Resveratrol
Institution
University of Louisville
Faculty Advisor/ Mentor
Carolyn M. Klinge
Abstract
Epidemiological studies have demonstrated that the consumption of polyphenolic-rich foods and beverages reduce the incidence of mortality and morbidity from coronary heart disease and arthrosclerosis. Moderate consumption of red wine has been under scrutiny due to its speculative role in the reduced incidence of coronary heart disease among the French, despite their high fat diet - termed the “French Paradox.” More specifically, the key polyphenol implicated in the cardioprotective effects of red wine is trans-resveratrol (trans-2,5,4’-trihydroxystilbene). Resveratrol is a phytoestrogen because it binds estrogen receptors (ER) alpha and beta, albeit with lower affinity than estradiol (E2). E2 has wellestablished cardioprotective effects including direct effects in endothelial cells (EC) through its genomic (transcription-dependent) and non-genomic (transcriptionindependent) activities. Previous studies in EC showed that nanomolar concentrations of E2 and resveratrol rapidly activate mitogen-activated phosphokinase (MAPK) signaling in an ER-dependent manner, leading to activation of endothelial nitric oxide synthase (eNOS) and the release of nitric oxide (NO) which is vasodilatory and vasoprotective. EC have caveolae that serve as anchoring sites for Src, components of the MAPK signaling pathway, and ERalpha. Specifically, caveolin-1, is responsible for the formation of the caveolae and is involved in the signaling cascade associated with NO release. This project tested the hypothesis that resveratrol, like E2, induces ERalphaSrc-Cav-1 interaction and phosphorylation in human umbilical vein endothelial cells. Results demonstrated that resveratrol, like E2, rapidly induced Src and ERalpha phosphorylation and interaction with Cav-1. These data support the hypothesis that resveratrol activates ERalpha and activation of a phosphorylation cascade leading to eNOS stimulation and NO release.
Role of Caveolae in Cardioprotective Activity of the Red Wine Polyphenol Resveratrol
Epidemiological studies have demonstrated that the consumption of polyphenolic-rich foods and beverages reduce the incidence of mortality and morbidity from coronary heart disease and arthrosclerosis. Moderate consumption of red wine has been under scrutiny due to its speculative role in the reduced incidence of coronary heart disease among the French, despite their high fat diet - termed the “French Paradox.” More specifically, the key polyphenol implicated in the cardioprotective effects of red wine is trans-resveratrol (trans-2,5,4’-trihydroxystilbene). Resveratrol is a phytoestrogen because it binds estrogen receptors (ER) alpha and beta, albeit with lower affinity than estradiol (E2). E2 has wellestablished cardioprotective effects including direct effects in endothelial cells (EC) through its genomic (transcription-dependent) and non-genomic (transcriptionindependent) activities. Previous studies in EC showed that nanomolar concentrations of E2 and resveratrol rapidly activate mitogen-activated phosphokinase (MAPK) signaling in an ER-dependent manner, leading to activation of endothelial nitric oxide synthase (eNOS) and the release of nitric oxide (NO) which is vasodilatory and vasoprotective. EC have caveolae that serve as anchoring sites for Src, components of the MAPK signaling pathway, and ERalpha. Specifically, caveolin-1, is responsible for the formation of the caveolae and is involved in the signaling cascade associated with NO release. This project tested the hypothesis that resveratrol, like E2, induces ERalphaSrc-Cav-1 interaction and phosphorylation in human umbilical vein endothelial cells. Results demonstrated that resveratrol, like E2, rapidly induced Src and ERalpha phosphorylation and interaction with Cav-1. These data support the hypothesis that resveratrol activates ERalpha and activation of a phosphorylation cascade leading to eNOS stimulation and NO release.