TY - JOUR AB - Oxidized low‑density lipoprotein (ox‑LDL) induces endothelial cell apoptosis and dysfunction. Statins are drugs that are clinically used to lower serum cholesterol levels, and they have been shown to exert vascular protective effects. In the present study, human umbilical vein endothelial cells were transfected with scramble control siRNA or siRNA specific for glutathione peroxidase (GPx)4 or cystine‑glutamate antiporter (xCT). MTT, Matrigel and Transwell assays were used to evaluate cell proliferation, tube formation and migration, respectively. The levels of TNF‑α, IL‑α, 4‑hydroxynonenal, GPx4 and xCT expression were detected by western blot analysis. It was demonstrated that ox‑LDL promoted cytokine production and reduced the proliferation, migration and angiogenesis of endothelial cells. It was also observed that ox‑LDL decreased GPx4 and xCT expression and induced ferroptosis. Furthermore, the inhibition of ferroptosis by deferoxamine mesylate attenuated ox‑LDL‑induced endothelial cell dysfunction and restored ox‑LDL‑decreased GPx4 and xCT expression. Consistent with these results, GPx4 and xCT knockdown by siRNA transfection aggravated ox‑LDL‑induced endothelial cell dysfunction and inhibition of proliferation. To the best of our knowledge, the present study was the first to discover that fluvastatin may protect endothelial cells from ox‑LDL‑induced ferroptosis and dysfunction. Furthermore, knockdown of GPx4 and xCT expression blunted the protective effects of fluvastatin on ox‑LDL‑treated endothelial cells. These data indicated a novel function of fluvastatin in the protection of endothelial cells from ox‑LDL‑induced ferroptosis, the mechanism of which involves the regulation of GPx4 and xCT. AD - Department of Cardiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China The College of Traditional Chinese Medicine, Datong University, Datong, Shanxi 037009, P.R. China AU - Li,Qing AU - Liu,Chang AU - Deng,Liang AU - Xie,Enrui AU - Yadav,Nishant AU - Tie,Yuanyuan AU - Cheng,Zheng AU - Deng,Jie DA - 2021/11/01 DO - 10.3892/etm.2021.10710 IS - 5 JO - Exp Ther Med KW - oxidized low‑density lipoprotein ferroptosis fluvastatin PY - 2021 SN - 1792-0981 1792-1015 SP - 1275 ST - Novel function of fluvastatin in attenuating oxidized low‑density lipoprotein‑induced endothelial cell ferroptosis in a glutathione peroxidase4‑ and cystine‑glutamate antiporter‑dependent manner T2 - Experimental and Therapeutic Medicine TI - Novel function of fluvastatin in attenuating oxidized low‑density lipoprotein‑induced endothelial cell ferroptosis in a glutathione peroxidase4‑ and cystine‑glutamate antiporter‑dependent manner UR - https://doi.org/10.3892/etm.2021.10710 VL - 22 ER -