ArticleAmerican journal of physiology. Heart and circulatory physiology2012
Epigenetic upregulation of p66shc mediates low-density lipoprotein cholesterol-induced endothelial cell dysfunction.
Article in American journal of physiology. Heart and circulatory physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
27 citing papers in PubMed, 57 citations in OpenAlex.
- The Impact of Modifiable Risk Factors on the Endothelial Cell Methylome and Cardiovascular Disease Development.Frontiers in bioscience (Landmark edition) · 2025Review
- SAHA inhibits lung fibroblast activation by increasing p66Shc expression epigenetically.Aging medicine (Milton (N.S.W)) · 2024Article
- Poly (ADP-ribose) Polymerase-1 modulations in the genesis of thrombosis.Journal of thrombosis and thrombolysis · 2024Review
- Molecular mechanisms of endothelial dysfunction in coronary microcirculation dysfunction.Journal of thrombosis and thrombolysis · 2023Review
- Endothelial Dysfunction in Cardiorenal Conditions: Implications of Endothelial Glucocorticoid Receptor-Wnt Signaling.International journal of molecular sciences · 2023Review
- Mitochondria in endothelial cells angiogenesis and function: current understanding and future perspectives.Journal of translational medicine · 2023Review
- Epigenetic modifications as therapeutic targets in atherosclerosis: a focus on DNA methylation and non-coding RNAs.Frontiers in cardiovascular medicine · 2023Review
- p66Shc in Cardiovascular Pathology.Cells · 2022Review
- Human SHC-transforming protein 1 and its isoforms p66shc: A novel marker for prediabetes.Journal of diabetes investigation · 2021Article
- Association of serum levels of antibodies against ALDOA and FH4 with transient ischemic attack and cerebral infarction.BMC neurology · 2021Article
- The Role of Histone Protein Acetylation in Regulating Endothelial Function.Frontiers in cell and developmental biology · 2021Review
- Article
- Roles and Mechanisms of DNA Methylation in Vascular Aging and Related Diseases.Frontiers in cell and developmental biology · 2021Review
- P66Shc and vascular endothelial function.Bioscience reports · 2019Review
- Machine learning algorithm-based risk prediction model of coronary artery disease.Molecular biology reports · 2018Article
- Loss of the adaptor protein ShcA in endothelial cells protects against monocyte macrophage adhesion, LDL-oxydation, and atherosclerotic lesion formation.Scientific reports · 2018Article
- WNT Signaling in Cardiac and Vascular Disease.Pharmacological reviews · 2018Review
- Probucol ameliorates renal injury in diabetic nephropathy by inhibiting the expression of the redox enzyme p66Shc.Redox biology · 2017Article
- New aspects of p66Shc in ischaemia reperfusion injury and other cardiovascular diseases.British journal of pharmacology · 2017Review
- p66Shc: A novel biomarker of tubular oxidative injury in patients with diabetic nephropathy.Scientific reports · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Hypercholesterolemia characterized by elevation of low-density lipoprotein (LDL) cholesterol is a major risk factor for atherosclerotic vascular disease. p66shc mediates hypercholesterolemia-induced endothelial dysfunction and atheromatous plaque formation. We asked if LDL upregulates endothelial p66shc via changes in the epigenome and examined the role of p66shc in LDL-stimulated endothelial cell dysfunction. Human LDL stimulates human p66shc promoter activity and p66shc expression in human endothelial cells. LDL leads to hypomethylation of two CpG dinucleotides and acetylation of histone 3 in the human p66shc promoter. These two CpG dinucleotides mediate LDL-stimulated p66shc promoter activity. Inhibition or knock down of DNA methyltransferases negates LDL-induced endothelial p66shc expression. p66shc mediates LDL-stimulated increase in expression of endothelial intercellular adhesion molecule-1 (ICAM1) and decrease in expression of thrombomodulin (TM). Mirroring these changes in ICAM1 and TM expression, p66shc mediates LDL-stimulated adhesion of monocytes to endothelial cells and plasma coagulation on endothelial cells. These findings indicate that LDL cholesterol upregulates human endothelial p66shc expression via hypomethylation of CpG dinucleotides in the p66shc promoter. Moreover, they show that LDL-stimulated p66shc expression mediates a dysfunctional endothelial cell surface, with proadhesive and procoagulant features.
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Registered trials
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.