Irisin/PPARα improves the ox-LDL-induced endothelial cell pyroptosis and inflammatory response

International Journal of Industrial Chemistry

مقالات آماده انتشار، پذیرفته شده، انتشار آنلاین از تاریخ 04 تیر 1401

نوع مقاله: research article

نویسندگان

Yujia Pan¹؛ Hangjun Ou¹؛ Xiang Wang²؛ Danan Liu^{* 3}

¹School of clinical medicine, Guizhou Medical University, Guiyang, Guizhou, 550004, China

²Department of Cardiology, Kaifeng people's Hospital of Henan Province, Kaifeng, Henan, 475000, China

³Department of Cardiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, China

چکیده

Atherosclerosis is an inflammatory disease associated with damaged endothelial cells. Pyroptosis is a newly discovered programmed cell death with inflammatory effects that plays a role during atherosclerosis progression. Irisin and PPARα regulate lipid metabolism and exert anti-inflammatory and cardiovascular protective effects. This study aimed to investigate whether Irisin plays a protective role in endothelial pyroptosis via the Irisin/PPARα signaling and explored the underlying mechanisms. In this study, HUVECs was treated with oxidized low-density lipoprotein (ox-LDL) to induce pyroptosis. Irisin significantly inhibited the ox-LDL-induced cell pyroptosis and reduced the expression of PPARα, NLRP3, caspase-1, GSDMD, IL-1β, and IL-18. In addition, Irisin reduced the expression of NF-κB p65, NF-κB p50, and inhibited IκBα phosphorylation. After treatment with the PPARα-specific inhibitor GW1647, the inhibition of Irisin on PPARα, NLRP3, caspase-1, GSDMD, IL-1β, IL-18, NF-κB p65, and NF-κB p50 was reversed, and IκBα phosphorylation was increased. Taken together, Irisin can improve the ox-LDL-induced pyroptosis by the NF-κB signaling pathway.

کلیدواژه‌ها

Atherosclerosis؛ pyroptosis؛ inflammation؛ endothelial cells؛ Irisin