ArticleThe Journal of experimental medicine2006
Antioxidants protect from atherosclerosis by a heme oxygenase-1 pathway that is independent of free radical scavenging.
Article in The Journal of experimental medicine, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
49 citing papers in PubMed, 2 syntheses or guidelines pooled it, 144 citations in OpenAlex.
- Flavonols reduce aortic atherosclerosis lesion area in apolipoprotein E deficient mice: A systematic review and meta-analysis.PloS one · 2017Pooled it
- Effects of probucol on restenosis after percutaneous coronary intervention: a systematic review and meta-analysis.PloS one · 2015Pooled it
- Heme Oxygenase-1, Cardiac Senescence, and Myocardial Infarction: A Critical Review of the Triptych.Cardiovascular drugs and therapy · 2025Review
- Eicosapentaenoic acid limits the more rapid oxidation of lipoprotein(a) compared with other apolipoprotein B particles.Cardiovascular research · 2025Article
- The therapeutic potential of probucol and probucol analogues in neurodegenerative diseases.Translational neurodegeneration · 2024Review
- Role of oxidative stress in calcific aortic valve disease and its therapeutic implications.Cardiovascular research · 2022Review
- Induction of Heme Oxygenase-1 Modifies the Systemic Immunity and Reduces Atherosclerotic Lesion Development in ApoE Deficient Mice.Frontiers in pharmacology · 2022Article
- Role of oxidative stress versus lipids in monocrotaline-induced pulmonary hypertension and right heart failure.Physiological reports · 2021Article
- Non-Transferrin-Bound Iron in the Spotlight: Novel Mechanistic Insights into the Vasculotoxic and Atherosclerotic Effect of Iron.Antioxidants & redox signaling · 2021Review
- Metformin directly suppresses atherosclerosis in normoglycaemic mice via haematopoietic adenosine monophosphate-activated protein kinase.Cardiovascular research · 2021Article
- Effects of fermented Sorghum bicolor L. Moench extract on inflammation and thickness in a vascular cell and atherosclerotic mice model.Journal of natural medicines · 2019Article
- Loss of heme oxygenase-1 accelerates mesodermal gene expressions during embryoid body development from mouse embryonic stem cells.Redox biology · 2018Article
- Heme Oxygenases in Cardiovascular Health and Disease.Physiological reviews · 2016Review
- Probucol inhibits LPS-induced microglia activation and ameliorates brain ischemic injury in normal and hyperlipidemic mice.Acta pharmacologica Sinica · 2016Article
- Endothelial HO-1 induction by model TG-rich lipoproteins is regulated through a NOX4-Nrf2 pathway.Journal of lipid research · 2016Article
- Synergistic Effects of Cilostazol and Probucol on ER Stress-Induced Hepatic Steatosis via Heme Oxygenase-1-Dependent Activation of Mitochondrial Biogenesis.Oxidative medicine and cellular longevity · 2016Article
- Probucol Protects Against Atherosclerosis Through Lipid-lowering and Suppressing Immune Maturation of CD11c+ Dendritic Cells in STZ-induced Diabetic LDLR-/- Mice.Journal of cardiovascular pharmacology · 2015Article
- Article
- Association of exhaled carbon monoxide with subclinical cardiovascular disease and their conjoint impact on the incidence of cardiovascular outcomes.European heart journal · 2014Observational
- New insights into intracellular locations and functions of heme oxygenase-1.Antioxidants & redox signaling · 2014Review
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oxidative stress is implicated in atherogenesis, yet most clinical trials with antioxidants, particularly vitamin E, have failed to protect against atherosclerotic diseases. A striking exception is probucol, which retards atherosclerosis in carotid arteries and restenosis of coronary arteries after angioplasty. Because probucol has in vitro cellular-protective effects independent of inhibiting lipid oxidation, we investigated the mode of action of probucol in vivo. We used three models of vascular disease: apolipoprotein E-deficient mice, a model of atherosclerosis; rabbit aortic balloon injury, a model of restenosis; and carotid injury in obese Zucker rats, a model of type 2 diabetes. Unexpectedly, we observed that the phenol moieties of probucol were insufficient, whereas its sulphur atoms were required for protection. Probucol and its sulphur-containing metabolite, but not a sulphur-free phenolic analogue, protected via cell-specific effects on inhibiting macrophage accumulation, stimulating reendothelialization, and inhibiting vascular smooth muscle cell proliferation. These processes were mediated via induction of heme oxygenase-1 (HO-1), an activity not shared by vitamin E. Our findings identify HO-1 as the molecular target of probucol. They indicate 2-electron rather than radical (1-electron) oxidants as important contributors to atherogenesis, and point to novel lead compounds for therapeutic intervention against atherosclerotic diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.