ArticleJournal of diabetes research2019
Advanced Glycation End-Products and Hyperglycemia Increase Angiopoietin-2 Production by Impairing Angiopoietin-1-Tie-2 System.
Article in Journal of diabetes research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 30 citations in OpenAlex.
- Therapeutic impact of vildagliptin vs. gliclazide on insulin resistance and advanced glycated end product levels in newly diagnosed Egyptian diabetics: a randomized controlled trial.European journal of clinical pharmacology · 2025Trial
- Association of Serum Angiopoietin-2 With Kidney Function Decline Among Participants in the Multiethnic Study of Atherosclerosis (MESA) Cohort.Kidney medicine · 2026Article
- Association between the oxidative balance score and all-cause and cardiovascular mortality in patients with cardiovascular-kidney-metabolic syndrome--a retrospective cohort study from the NHANES.BMC cardiovascular disorders · 2025Article
- Role of Tie-2 Axis in Sepsis: A Potential Therapeutic Target.Journal of cellular and molecular medicine · 2025Review
- Tie2-mediated CBL ubiquitination of EGFR underlies ultrasound-responsive silk fibroin/graphene oxide hydrogel-troxerutin therapy for intervertebral disc degeneration.Materials today. Bio · 2025Article
- Combination ofInternational journal of molecular sciences · 2025Article
- The positive implication of natural antioxidants on oxidative stress-mediated diabetes mellitus complications.Journal, genetic engineering & biotechnology · 2024Review
- Angiopoietin II in Critically Ill Septic Patients: A Post Hoc Analysis of the DRAK Study.Biomedicines · 2024Article
- Mechanisms of Flavonoids and Their Derivatives in Endothelial Dysfunction Induced by Oxidative Stress in Diabetes.Molecules (Basel, Switzerland) · 2024Review
- The role of oxidative stress in diabetes mellitus-induced vascular endothelial dysfunction.Cardiovascular diabetology · 2023Review
- Research Trends in Advanced Glycation End Products and Obesity: Bibliometric Analysis.Nutrients · 2022Article
- Heterozygous Loss of KRIT1 in Mice Affects Metabolic Functions of the Liver, Promoting Hepatic Oxidative and Glycative Stress.International journal of molecular sciences · 2022Article
- Emerging therapeutic potential of adeno-associated virus-mediated gene therapy in liver fibrosis.Molecular therapy. Methods & clinical development · 2022Review
- Diabesity in Elderly Cardiovascular Disease Patients: Mechanisms and Regulators.International journal of molecular sciences · 2022Review
- Angiopoietin2-mediated caveolin1 phosphorylation regulating transcytosis of renal tubular epithelial cell contributes to the occurrence of albuminuria under high glucose exposure.Journal of translational medicine · 2022Article
- Role of Glucose-Lowering Medications in Erectile Dysfunction.Journal of clinical medicine · 2021Review
- Engeletin protects against cerebral ischemia/reperfusion injury by modulating the VEGF/vasohibin and Ang-1/Tie-2 pathways.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The angiopoietin-Tie-2 system plays a crucial role in the maintenance of endothelial integrity. Hyperglycemia and advanced glycation end-products (AGEs) are involved in endothelial cell dysfunction responsible of the pathogenesis of microvascular complications of diabetes. Here, we investigated whether glycated serum (GS) or hyperglycemia (HG) affect the angiopoietin-Tie-2 system in the microvascular endothelial cells HMEC-1. We found that culture for 5 days in the presence of AGEs and HG (alone or in combination) decreased cell proliferation, increased reactive oxygen species (ROS) production, and reduced ratio between the oxidized and the reduced form of glutathione. Since angiopoietin-1 (Ang-1) signaling regulates angiopoietin-2 (Ang-2) expression through inactivation of the forkhead transcription factor FoxO1, we investigated intracellular signaling of Ang-1 and expression of Ang-2. HG and AGEs reduced phosphorylation of Akt and abrogated phosphorylation of FoxO1 induced by Ang-1 without affecting neither Tie-2 expression nor its activation. Furthermore, AGEs and/or HG induced nuclear translocation of FoxO1 and increased Ang-2 production. In conclusion, we demonstrated that both hyperglycemia and AGEs affect the angiopoietin-Tie-2 system by impairing Ang-1/Tie-2 signaling and by increasing Ang-2 expression. These results suggest that therapeutic strategies useful in preventing or delaying the onset of diabetic vascular complications should be aimed to preserve Ang-1 signaling.
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