ArticleLife sciences2014
Dual endothelin receptor antagonism with bosentan reverses established vascular remodeling and dysfunctional angiogenesis in diabetic rats: relevance to glycemic control.
Article in Life sciences, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Dual endothelin receptor antagonism increases resting energy expenditure in people with increased adiposity.American journal of physiology. Endocrinology and metabolism · 2022Trial
- Vascular contributions to cognitive impairment/dementia in diabetes: role of endothelial cells and pericytes.American journal of physiology. Cell physiology · 2022Review
- Impact of diabetes and ischemic stroke on the cerebrovasculature: A female perspective.Neurobiology of disease · 2022Review
- Endothelin-1 (ET-1) promotes a proinflammatory microglia phenotype in diabetic conditions.Canadian journal of physiology and pharmacology · 2020Article
- Histomorphological, VEGF and TGF-β immunoexpression changes in the diabetic rats' ovary and the potential amelioration following treatment with metformin and insulin.Journal of molecular histology · 2020Article
- Endothelium-dependent impairments to cerebral vascular reactivity with type 2 diabetes mellitus in the Goto-Kakizaki rat.American journal of physiology. Regulatory, integrative and comparative physiology · 2019Article
- Brain Vasculature and Cognition.Arteriosclerosis, thrombosis, and vascular biology · 2019Review
- Inhibition of Ephrin-B2 in brain pericytes decreases cerebral pathological neovascularization in diabetic rats.PloS one · 2019Article
- Metformin restores electrophysiology of small conductance calcium-activated potassium channels in the atrium of GK diabetic rats.BMC cardiovascular disorders · 2018Article
- Impact of Metabolic Diseases on Cerebral Circulation: Structural and Functional Consequences.Comprehensive Physiology · 2018Review
- Endothelin Confers Protection against High Glucose-Induced Neurotoxicity via Alleviation of Oxidative Stress.The Journal of pharmacology and experimental therapeutics · 2017Article
- Enhanced VEGF signalling mediates cerebral neovascularisation via downregulation of guidance protein ROBO4 in a rat model of diabetes.Diabetologia · 2017Article
- Article
- Linagliptin treatment improves cerebrovascular function and remodeling and restores reduced cerebral perfusion in Type 2 diabetes.American journal of physiology. Regulatory, integrative and comparative physiology · 2016Article
- Diabetes-mediated middle cerebral artery remodeling is restored by linagliptin: Interaction with the vascular smooth muscle cell endothelin system.Life sciences · 2016Article
- Relationship of endothelin-1 and NLRP3 inflammasome activation in HT22 hippocampal cells in diabetes.Life sciences · 2016Article
- Linagliptin attenuates diabetes-induced cerebral pathological neovascularization in a blood glucose-independent manner: Potential role of ET-1.Life sciences · 2016Article
- D-optimal Design for Preparation and Optimization of Fast Dissolving Bosentan Nanosuspension.Advanced pharmaceutical bulletin · 2016Article
- Vasculopathy in scleroderma.Seminars in immunopathology · 2015Review
- Endothelin receptor blockade ameliorates vascular fragility in endothelial cell-specific Fli-1-knockout mice by increasing Fli-1 DNA binding ability.Arthritis & rheumatology (Hoboken, N.J.) · 2015Article
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Authors and funding
4 authors.
Funding
Abstract
aimsWe have shown that diabetes causes cerebrovascular remodeling in part by the activation of the endothelin (ET-1) system in a glucose-dependent manner. We also reported increased yet dysfunctional cerebral angiogenesis in diabetes. Here, we tested the hypothesis that dual ET-1 receptor antagonism or glycemic control can reverse already established diabetes-induced vascular remodeling and neovascularization. MAIN
methods18-week non-obese type-2 diabetic Goto-Kakizaki (GK) were treated with vehicle, metformin (300 mg/kg/day) or bosentan (100 mg/kg/day) for 4 weeks by oral gavage and compared to 10 and 18-weeks GK rats. Isolated middle cerebral artery (MCA) lumen diameter (LD), media thickness (MT), media:lumen (M:L) ratio, and cross-sectional area (CSA) were measured using pressurized arteriograph. Assessment of remodeling and angiogenesis in the brain parenchyma was achieved by three-dimensional reconstruction of fluorescently labeled images of the vasculature acquired by confocal microscopy, and measurement of neovascularization indices including vascular volume and surface area, branch density and tortuosity. KEY
findingsMCA remodeling (increased M:L ratio and CSA, but decreased LD) occurred by 18 weeks and did not progress by 22 weeks in diabetic GK rats. Metformin and bosentan partially corrected large artery remodeling. Both treatments significantly reduced all indices of neovascularization compared to untreated diabetic rats. SIGNIFICANCE: Glycemic control or ET-1 antagonism can partially reverse diabetes-induced cerebrovascular remodeling and neovascularization. These results strongly suggest that either approach offers a therapeutic benefit and combination treatments need to be tested.
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