ArticleBioMed research international2014
Oxidative stress induces endothelial cell senescence via downregulation of Sirt6.
Article in BioMed research international, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.
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Who cites it
71 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.
- Antioxidant strategies against cellular senescence: unveiling the power of synthetic versus natural antioxidants in a systematic review.Frontiers in aging · 2025Pooled it
- CIRP Promotes Redox-Inflammatory Endothelial Injury in High-Fat Diet-Fed ApoEAntioxidants (Basel, Switzerland) · 2026Article
- LIN28A blocks the EndMT process of high glucose-induced HRMECs by stabilizing SIRT6 mRNA.Journal of diabetes investigation · 2026Article
- Integrative multi-omics analysis of macrophage polarization-related genes in atherosclerosis development.Clinical epigenetics · 2026Article
- The Role and Mechanism of Gut Microbiota and Metabolites in Vascular Calcification.International journal of molecular sciences · 2026Review
- 4-Phenylbutyric Acid Reduces the Proliferation in Colon Cancer Cell Lines Through Modulating the Cell Cycle Regulatory Genes: An In Silico and In Vitro Approach.Cancer reports (Hoboken, N.J.) · 2025Article
- NADCommunications biology · 2025Article
- SGLT2 inhibitors as a novel senotherapeutic approach.npj aging · 2025Review
- Senescence of endothelial cells promotes phenotypic changes in adventitial fibroblasts: possible implications for vascular aging.Molecular and cellular biochemistry · 2025Article
- Inhibition of the E3 ligase UBR5 stabilizes TERT and protects vascular organoids from oxidative stress.Journal of translational medicine · 2024Article
- Epigenetic mechanism of SET7/9-mediated histone methylation modification in high glucose-induced ferroptosis in retinal pigment epithelial cells.Journal of bioenergetics and biomembranes · 2024Article
- Liraglutide prevents cellular senescence in human retinal endothelial cells (HRECs) mediated by SIRT1: an implication in diabetes retinopathy.Human cell · 2024Article
- ROS-Induced Endothelial Dysfunction in the Pathogenesis of Atherosclerosis.Aging and disease · 2024Review
- Circular RNAs: Regulators of endothelial cell dysfunction in atherosclerosis.Journal of molecular medicine (Berlin, Germany) · 2024Review
- SIRT6 Protects Against Lipopolysaccharide-Induced Inflammation in Human Pulmonary Lung Microvascular Endothelial Cells.Inflammation · 2024Article
- Identifying the stability of housekeeping genes to be used for the quantitative real-time PCR normalization in retinal tissue of streptozotocin-induced diabetic rats.International journal of ophthalmology · 2024Article
- Activation of aryl hydrocarbon receptor (AhR) in Alzheimer's disease: role of tryptophan metabolites generated by gut host-microbiota.Journal of molecular medicine (Berlin, Germany) · 2023Review
- Shedding light on structure, function and regulation of human sirtuins: a comprehensive review.3 Biotech · 2023Review
- Mechanisms and consequences of endothelial cell senescence.Nature reviews. Cardiology · 2023Review
- Downregulation of SIRT6 and NMNAT2 is associated with proliferative diabetic retinopathy.Molecular vision · 2023Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Accumulating evidence has shown that diabetes accelerates aging and endothelial cell senescence is involved in the pathogenesis of diabetic vascular complications, including diabetic retinopathy. Oxidative stress is recognized as a key factor in the induction of endothelial senescence and diabetic retinopathy. However, specific mechanisms involved in oxidative stress-induced endothelial senescence have not been elucidated. We hypothesized that Sirt6, which is a nuclear, chromatin-bound protein critically involved in many pathophysiologic processes such as aging and inflammation, may have a role in oxidative stress-induced vascular cell senescence. Measurement of Sirt6 expression in human endothelial cells revealed that H2O2 treatment significantly reduced Sirt6 protein. The loss of Sirt6 was associated with an induction of a senescence phenotype in endothelial cells, including decreased cell growth, proliferation and angiogenic ability, and increased expression of senescence-associated β-galactosidase activity. Additionally, H2O2 treatment reduced eNOS expression, enhanced p21 expression, and dephosphorylated (activated) retinoblastoma (Rb) protein. All of these alternations were attenuated by overexpression of Sirt6, while partial knockdown of Sirt6 expression by siRNA mimicked the effect of H2O2. In conclusion, these results suggest that Sirt6 is a critical regulator of endothelial senescence and oxidative stress-induced downregulation of Sirt6 is likely involved in the pathogenesis of diabetic retinopathy.
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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.