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Issue 9, 2019
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The protective effect of hydroxytyrosol acetate against inflammation of vascular endothelial cells partly through the SIRT6-mediated PKM2 signaling pathway

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Abstract

Hydroxytyrosol acetate (HT-AC), a polyphenolic compound in olive oil, exerts an anti-inflammatory effect on murine collagen-induced arthritis. However, the effect of HT-AC on inflammatory response in cardiovascular disease remains unclear. Thus, in this study, we aimed to investigate the effect of HT-AC on the inflammation response of vascular endothelial cells and the related molecular mechanism. Our results showed that HT-AC inhibited the inflammatory response in hypercholesterolemic mice and tumor necrosis factor (TNF)-stimulated HUVECs. Meanwhile, HT-AC also up-regulated SIRT6 expression in hypercholesterolemic mice and HUVECs. To further investigate whether SIRT6 is involved in the regulation of endothelial inflammatory response by HT-AC, endothelium-specific Sirt6 knockout (Sirt6endo−/−) mice were used. Our study found that Sirt6endo−/− abolished the inhibition of inflammatory response by HT-AC in the thoracic aorta of hypercholesterolemic mice. In vitro study also showed that knockdown of SIRT6 reduced the inhibition of inflammatory response by HT-AC, whereas overexpression of SIRT6 augmented the inhibition of inflammatory response by HT-AC in HUVECs. Further study demonstrated that HT-AC exerts its anti-inflammatory effect partly via the SIRT6-mediated PKM2 signaling pathway. In addition, HT-AC inhibited TNF-induced inflammatory response through the TNF receptor superfamily member 1A (TNFRSF1A) signaling pathway. These findings indicate that HT-AC regulates the vascular endothelial inflammatory response partly through the TNFRSF1A/SIRT6/PKM2-mediated signaling pathway.

Graphical abstract: The protective effect of hydroxytyrosol acetate against inflammation of vascular endothelial cells partly through the SIRT6-mediated PKM2 signaling pathway

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Article information


Submitted
20 Mar 2019
Accepted
08 Aug 2019
First published
09 Aug 2019

Food Funct., 2019,10, 5789-5803
Article type
Paper

The protective effect of hydroxytyrosol acetate against inflammation of vascular endothelial cells partly through the SIRT6-mediated PKM2 signaling pathway

F. Yao, G. Yang, Y. Xian, G. Wang, Z. Zheng, Z. Jin, Y. Xie, W. Wang, J. Gu and R. Lin, Food Funct., 2019, 10, 5789
DOI: 10.1039/C9FO00586B

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