CTRP13 attenuates atherosclerosis by inhibiting endothelial cell ferroptosis via activating GCH1

作者：Jie Du, Xinxin Zhu, Youqi Zhang, Xingtao Huang, Xuedong Wang, Fan Yang, Hongyuan Xia, Jingbo Hou · 发表于：International Immunopharmacology · 年份：2024 · DOI：10.1016/j.intimp.2024.113617 · 被引用次数：15 · 研究领域：Ferroptosis and cancer prognosis、MicroRNA in disease regulation、Cancer, Lipids, and Metabolism

• The antioxidative activities of CTRP13 alleviate ox-LDL-induced endothelial cell ferroptosis. • CTRP13 reduced the progression of atherosclerosis and increases the stability of atherosclerotic plaques. • CTRP13 treatment reduced ox-LDL-induced mitochondrial oxidative stress. • CTRP13 exerted its anti-atherosclerosis effects via GCH1-BH4 pathway activation. C1q/TNF-related protein 13 (CTRP13) is a secreted adipokine that has been shown to play an important role in a variety of cardiovascular diseases. However, the effect of CTRP13 on ferroptosis of endothelial cells and its underlying mechanism remain unclear. In the present study, we analyzed the effects of CTRP13 on endothelial dysfunction in high-lipid-induced ApoE −/− mice and ox-LDL-induced mouse aortic endothelial cells (MAECs). In vivo experiment: Male ApoE −/− mice fed high fat were given C1ql3 gene overexpression adeno-associated virus. The atherosclerotic plaque size, lipid content, collagen fiber proportion and iron deposition level were measured. In vitro, CTRP13 combined with ox-LDL was used to pretreat MAECs to detect cell survival rate, lipid peroxidation, iron ion deposition and mitochondrial level. In this study, CTRP13 was found to inhibit ferroptosis of endothelial cells, demonstrated by up-regulated the expression of ferroptosis protective protein glutathione Peroxidase 4 (GPX4), and decreased the expression of acyl-CoA synthetase long-chain family member 4 (ACSL4) protein. Mechanistically, gtp cyclohydro...