ArticleDiabetologia2010
The endothelin receptor antagonist avosentan ameliorates nephropathy and atherosclerosis in diabetic apolipoprotein E knockout mice.
Article in Diabetologia, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 79 citations in OpenAlex.
- Effects of Niaoduqing Particles () on Delaying Progression of Renal Dysfunction: A Post-trial, Open-Label, Follow-up Study.Chinese journal of integrative medicine · 2019Trial
- Mechanism of protective actions of sparsentan in the kidney: lessons from studies in models of chronic kidney disease.Clinical science (London, England : 1979) · 2024Review
- Population pharmacokinetic analysis of sparsentan in healthy volunteers and patients with focal segmental glomerulosclerosis.CPT: pharmacometrics & systems pharmacology · 2023Article
- Phosphatidylinositol metabolism of the renal proximal tubule S3 segment is disturbed in response to diabetes.Scientific reports · 2023Article
- Endothelial reactive oxygen-forming NADPH oxidase 5 is a possible player in diabetic aortic aneurysm but not atherosclerosis.Scientific reports · 2022Article
- Adverse renal effects of NLRP3 inflammasome inhibition by MCC950 in an interventional model of diabetic kidney disease.Clinical science (London, England : 1979) · 2022Article
- Stem cell-derived and circulating exosomal microRNAs as new potential tools for diabetic nephropathy management.Stem cell research & therapy · 2022Review
- Endothelin-targeted new treatments for proteinuric and inflammatory glomerular diseases: focus on the added value to anti-renin-angiotensin system inhibition.Pediatric nephrology (Berlin, Germany) · 2021Review
- Endothelium-restricted endothelin-1 overexpression in type 1 diabetes worsens atherosclerosis and immune cell infiltration via NOX1.Cardiovascular research · 2021Article
- Processed foods drive intestinal barrier permeability and microvascular diseases.Science advances · 2021Article
- Disparate Effects of Diabetes and Hyperlipidemia on Experimental Kidney Disease.Frontiers in physiology · 2020Article
- Endothelial or vascular smooth muscle cell-specific expression of human NOX5 exacerbates renal inflammation, fibrosis and albuminuria in the Akita mouse.Diabetologia · 2019Article
- Characterising an Alternative Murine Model of Diabetic Cardiomyopathy.Frontiers in physiology · 2019Article
- Lipoxins Regulate the Early Growth Response-1 Network and Reverse Diabetic Kidney Disease.Journal of the American Society of Nephrology : JASN · 2018Article
- TRAF3IP2 mediates high glucose-induced endothelin-1 production as well as endothelin-1-induced inflammation in endothelial cells.American journal of physiology. Heart and circulatory physiology · 2018Article
- Combined NOX1/4 inhibition with GKT137831 in mice provides dose-dependent reno- and atheroprotection even in established micro- and macrovascular disease.Diabetologia · 2017Article
- Dual inhibition of renin-angiotensin-aldosterone system and endothelin-1 in treatment of chronic kidney disease.American journal of physiology. Regulatory, integrative and comparative physiology · 2016Review
- Podocyte-specific Nox4 deletion affords renoprotection in a mouse model of diabetic nephropathy.Diabetologia · 2016Article
- Endothelin Blockade in Diabetic Kidney Disease.Journal of clinical medicine · 2015Review
- Diabetic Kidney Disease: Pathophysiology and Therapeutic Targets.Journal of diabetes research · 2015Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisThere is convincing evidence that the endothelin system contributes to diabetic nephropathy and cardiovascular disease. This study aimed to assess the effects of the non-peptidergic endothelin receptor A (ETA) antagonist avosentan in a mouse model of accelerated diabetic nephropathy and atherosclerosis in comparison with the ACE inhibitor, quinapril.
methodsApolipoprotein E (Apoe) knockout (KO) mice (n = 20 per group, five groups) were randomised to the following groups: non-diabetic controls and streptozotocin-induced diabetic animals gavaged daily for 20 weeks with placebo, avosentan (high dose: 30 mg/kg, or low dose: 10 mg/kg) or quinapril (given in drinking water, 30 mg/kg).
resultsBP was unchanged by avosentan treatment but decreased with quinapril treatment. Diabetes-associated albuminuria was significantly attenuated by high-dose avosentan after 10 and 20 weeks of treatment. Diabetic animals showed a decreased creatinine clearance, which was normalised by avosentan treatment. In diabetic mice, high-dose avosentan treatment significantly attenuated the glomerulosclerosis index, mesangial matrix accumulation, glomerular accumulation of the matrix proteins collagen IV, and renal expression of genes encoding connective tissue growth factor, vascular endothelial growth factor, transforming growth factor beta and nuclear factor kappaB (p65 subunit). Furthermore, high-dose avosentan treatment was also associated with reduced expression of the genes for ETA, ETB and angiotensin receptor 1. The renoprotective effects of avosentan were comparable or superior to those observed with quinapril. High-dose avosentan also significantly attenuated diabetes-associated aortic atherosclerosis in Apoe KO mice and reduced macrophage infiltration and aortic nitrotyrosine expression. CONCLUSIONS/
interpretationThis study demonstrates that ETA blockade with avosentan may provide an alternate therapeutic strategy for the treatment of diabetic micro- and macrovascular complications.
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