Hydroxytyrosol regulates the autophagy of vascular adventitial fibroblasts through the SIRT1-mediated signaling pathway.
Hydroxytyrosol (HT), a phenolic compound in olive oil, exerts an anti-inflammatory effect in cardiovascular diseases. Recent studies found that autophagy was a therapeutic target of diseases. However, the effect of HT on autophagy in vascular adventitial fibroblasts (VAFs) remains unknown. Thus, in this study, we aimed to determine the effect of HT on cell autophagy and related signaling pathway and whether HT regulates the inflammatory response through autophagy in VAFs. Our results showed that HT promoted cell autophagy by increasing the conversion of LC3 and Beclin1 expression and the autophagic flux in VAFs stimulated with tumor necrosis factor-α (TNF-α). HT also upregulated the expression of the deacetylase sirtuin 1 (SIRT1) protein and mRNA compared with the TNF-α group. The molecular docking studies showed the good compatibility between HT and SIRT1, indicating that HT might act through SIRT1. Further study found that HT regulated autophagy through SIRT1-mediated Akt/mTOR suppression in VAFs. In addition, HT inhibited TNF-α-induced inflammatory response in VAFs through SIRT1. Furthermore, the study showed that HT inhibited the inflammatory response of VAFs through autophagy. These findings indicate that HT regulates the autophagy of VAFs through SIRT1-mediated Akt/mTOR suppression and then inhibits the inflammatory response of VAFs.
['Wang|Weirong|W|', 'Jing|Ting|T|', 'Yang|Xiaofeng|X|', 'He|Yanhao|Y|', 'Wang|Bo|B|', 'Xiao|Yunfang|Y|', 'Shang|Chenxu|C|', 'Zhang|Jiye|J|', 'Lin|Rong|R|']
D063194:Adventitia D000818:Animals D001343:Autophagy D005347:Fibroblasts D007249:Inflammation D008297:Male D008954:Models, Biological D010626:Phenylethyl Alcohol D051057:Proto-Oncogene Proteins c-akt D017207:Rats, Sprague-Dawley D015398:Signal Transduction D056564:Sirtuin 1 D058570:TOR Serine-Threonine Kinases D014409:Tumor Necrosis Factor-alpha D015854:Up-Regulation
hydroxytyrosol autophagie autophagie vascular adventitial fibroblasts SIRT1 Akt/mTOR autophagy fibroblastes de l’adventice vasculaire inflammation