Caveolae and caveolin-1 as targets of dietary polyphenols for protection against vascular endothelial dysfunction

抄録

Caveolae, consisting of caveolin-1 proteins, are ubiquitously present in endothelial cells and contribute to normal cardio­vascular functions by acting as a platform for cellular signaling pathways as well as transcytosis and endocytosis. However, caveolin-1 is thought to have a proatherogenic role by inhibiting endothelial nitric oxide synthase activity and Nrf2 activation, or by promoting inflammation through NF-κB activation. Dietary polyphenols were suggested to exert anti-atherosclerotic effects by a mechanism involving the inhibition of endothelial dysfunc­tion, by which they can regulate redox-sensitive signaling pathways in relation to NF-κB and Nrf2 activation. Some monomeric polyphenols and microbiota-derived catabolites from monomeric polyphenols or polymeric tannins might be respon­sible for the inhibition, because they can be transferred into the circulation from the digestive tract. Several polyphenols were reported to modulate caveolin-1 expression or its localization in caveolae. Therefore, we hypothesized that circulating poly­phenols affect caveolae functions by altering its structure leading to the release of caveolin-1 from caveolae, and attenuating redox-sensitive signaling pathway-dependent caveolin-1 over­expres­sion. Further studies using circulating polyphenols at a physio­logically relevant level are necessary to clarify the mechanism of action of dietary polyphenols targeting caveolae and caveolin-1.