ArticlePloS one2021
A small-molecule inhibitor of hypoxia-inducible factor prolyl hydroxylase improves obesity, nephropathy and cardiomyopathy in obese ZSF1 rats.
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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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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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Effect of roxadustat on lowering blood lipids in peritoneal dialysis patients with anemia.Renal failure · 2025Trial
- Noradrenergic regulation of skeletal muscle oxygen pressures: Impact of heart failure with preserved ejection fraction and heat therapy.Experimental physiology · 2026Article
- Hypoxia, ROS, and HIF Signaling in I/R Injury: Implications and Future Prospects.Antioxidants (Basel, Switzerland) · 2026Review
- Roxadustat as a Hypoxia-Mimetic Agent: Erythropoietic Mechanisms, Bioanalytical Detection, and Regulatory Considerations in Sports Medicine.Current issues in molecular biology · 2025Review
- N-terminal pro-brain natriuretic peptide and cardiorenal outcome in patients with anaemia in chronic kidney disease.ESC heart failure · 2025Observational
- Roxadustat regulates the cell cycle and inhibits proliferation of mesangial cells via the hypoxia-inducible factor-1α/P53/P21 pathway.Frontiers in cell and developmental biology · 2025Article
- Targeting hypoxia-inducible factors: therapeutic opportunities and challenges.Nature reviews. Drug discovery · 2024Review
- Multimodal Imaging Reveals that Sustained Inhibition of HIF-Prolyl Hydroxylases Induces Opposing Effects on Right and Left Ventricular Function in Healthy Rats.Molecular imaging and biology · 2024Article
- Searching for Effective Treatments in HFpEF: Implications for Modeling the Disease in Rodents.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Rodent models to study type 1 and type 2 diabetes induced human diabetic nephropathy.Molecular biology reports · 2023Review
- Hypoxia-inducible factors and essential hypertension: narrative review of experimental and clinical data.Pharmacological reports : PR · 2023Review
- Comparison between the influence of roxadustat and recombinant human erythropoietin treatment on blood pressure and cardio-cerebrovascular complications in patients undergoing peritoneal dialysis.Frontiers in medicine · 2023Article
- Review
- The Role of Hypoxia-Inducible Factor-1 Alpha in Renal Disease.Molecules (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Prolyl hydroxylase (PH) enzymes control the degradation of hypoxia-inducible factor (HIF), a transcription factor known to regulate erythropoiesis, angiogenesis, glucose metabolism, cell proliferation, and apoptosis. HIF-PH inhibitors (HIF-PHIs) correct anemia in patients with renal disease and in animal models of anemia and kidney disease. However, the effects of HIF-PHIs on comorbidities associated with kidney disease remain largely unknown. We evaluated the effects of the HIF-PHI FG-2216 in obese ZSF1 (Ob-ZSF1) rats, an established model of kidney failure with metabolic syndrome. Following unilateral nephrectomy (Nx) at 8 weeks of age, rats were treated with 40 mg/kg FG-2216 or vehicle by oral gavage three times per week for up to 18 weeks. FG-2216 corrected blood hemoglobin levels and improved kidney function and histopathology in Nx-Ob-ZSF1 rats by increasing the glomerular filtration rate, decreasing proteinuria, and reducing peritubular fibrosis, tubular damage, glomerulosclerosis and mesangial expansion. FG-2216 increased renal glucose excretion and decreased body weight, fat pad weight, and serum cholesterol in Nx-Ob-ZSF1 rats. Additionally, FG-2216 corrected hypertension, improved diastolic and systolic heart function, and reduced cardiac hypertrophy and fibrosis. In conclusion, the HIF-PHI FG-2216 improved renal and cardiovascular outcomes, and reduced obesity in a rat model of kidney disease with metabolic syndrome. Thus, in addition to correcting anemia, HIF-PHIs may provide renal and cardiac protection to patients suffering from kidney disease with metabolic syndrome.
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