ArticleExperimental and therapeutic medicine2021
Novel function of fluvastatin in attenuating oxidized low-density lipoprotein-induced endothelial cell ferroptosis in a glutathione peroxidase4- and cystine-glutamate antiporter-dependent manner.
Article in Experimental and therapeutic medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 17 citations in OpenAlex.
- Research progress of ferroptosis in gynecological diseases.Annals of medicine · 2026Review
- Programmed Cell Death of Endothelial Cells in Ischemic Heart Disease: Mechanism and Potential Cell and Gene Therapeutic Prospects.Bioengineering (Basel, Switzerland) · 2026Review
- Lipophilic Statins Deplete GPX4 to Promote Ferroptosis and Sensitize Cancer Cells to Immune Checkpoint Blockade.Molecular cancer therapeutics · 2026Article
- OxLDL-induced ferroptosis and pyroptosis in atherosclerosis: a mini review.Frontiers in immunology · 2026Review
- Metabolic alterations and redox homeostasis in ferroptosis: emerging mechanisms and therapeutic implications.Archives of medical science : AMS · 2026Article
- Phytoconstituents-mediated Targeting of Ferroptosis for the Treatment of Cardiovascular Disease.Current cardiology reviews · 2026Review
- Fluvastatin suppresses hemin-induced cell death, reactive oxygen species generation, and elevated labile iron pool.Hematology, transfusion and cell therapy · 2024Article
- Article
- Design, synthesis, and evaluation of novel ferrostatin derivatives for the prevention of HG-induced VEC ferroptosis.RSC medicinal chemistry · 2024Article
- Ferroptosis in cancer: From molecular mechanisms to therapeutic strategies.Signal transduction and targeted therapy · 2024Review
- CTRP13 Mitigates Endothelial Cell Ferroptosis via the AMPK/KLF4 Pathway: Implications for Atherosclerosis Protection.Medical science monitor : international medical journal of experimental and clinical research · 2024Article
- Advances on the Role of Ferroptosis in Ionizing Radiation Response.Current pharmaceutical biotechnology · 2024Review
- Ferroptosis of Endothelial Cells in Vascular Diseases.Nutrients · 2022Review
- From Iron Metabolism to Ferroptosis: Pathologic Changes in Coronary Heart Disease.Oxidative medicine and cellular longevity · 2022Review
- Research Progress of Ferroptosis in Adiposity-Based Chronic Disease (ABCD).Oxidative medicine and cellular longevity · 2022Review
- Atorvastatin Inhibits Ferroptosis of H9C2 Cells by regulatingSMAD7/Hepcidin Expression to Improve Ischemia-Reperfusion Injury.Cardiology research and practice · 2022Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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Registered trials
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