ReviewJACC. Basic to translational science2020
Mutual Antagonism of Hypoxia-Inducible Factor Isoforms in Cardiac, Vascular, and Renal Disorders.
Review in JACC. Basic to translational science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
57 citing papers in PubMed, 2 syntheses or guidelines pooled it, 98 citations in OpenAlex.
- Effect of sodium-glucose cotransporter 2 inhibitors on hemoglobin and hematocrit levels in type 2 diabetes: a systematic review and meta-analysis.International urology and nephrology · 2022Pooled it
- Efficacy and Safety of Roxadustat in Patients with Chronic Kidney Disease: An Updated Meta-Analysis of Randomized Controlled Trials including 6,518 Patients.BioMed research international · 2022Pooled it
- How do SGLT2 inhibitors protect the kidney? A mediation analysis of the EMPA-REG OUTCOME trial.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Trial
- Infantile Cocktail of Erythropoietin and Melatonin Restores Gait in Adult Rats with Preterm Brain Injury.Developmental neuroscience · 2022Trial
- Reduction of estimated fluid volumes following initiation of empagliflozin in patients with type 2 diabetes and cardiovascular disease: a secondary analysis of the placebo-controlled, randomized EMBLEM trial.Cardiovascular diabetology · 2021Trial
- Hypoxia-Driven Mechanisms in Ischemic Heart Failure: A Bioinformatics, Machine Learning and Bayesian Network Study.Cardiovascular toxicology · 2026Article
- Article
- Therapeutic Targets for Hepatic Fibrosis Driven by Hypoxia-Mediated Hepatic Stellate Cell Activation.Biomolecules · 2026Review
- Decoding cardiorenal crosstalk: Intercellular communication mechanisms and therapeutic insights in cardiorenal syndrome.iScience · 2026Review
- VHL-recruiting PROTAC attenuates AKI-CKD transition via simultaneous degradation of Smad3 and stabilization of HIF-2α.Cell death & disease · 2026Article
- Sodium-glucose cotransporter-2 inhibitors and sepsis: a story with two tails or with one tail?Inflammopharmacology · 2026Review
- A Brief Description of the Cellular Mechanisms Involved in Cardiac Chemical Hypoxia.Cardiovascular toxicology · 2026Review
- Hypoxia-inducible factors in the immunometabolism of metabolic dysfunction-associated steatotic liver disease (MASLD): molecular mechanisms and therapeutic implications.Frontiers in physiology · 2026Article
- HIF-mediated hierarchical hypoxic adaptation, a novel paradigm in heart failure pathogenesis: is there a role for targeted therapies?Frontiers in pharmacology · 2026Review
- The Inflammatory Milieu Exacerbates Anemia of Chronic Kidney Disease: From the Gut-Kidney Axis to Bone Marrow Hematopoiesis Inhibition.Kidney & blood pressure research · 2026Review
- PHD2 Deletion in CD8Hypertension (Dallas, Tex. : 1979) · 2025Article
- Safety of Roxadustat in Chronic Kidney Disease Patients: An Updated Systematic Review and Meta-Analysis.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Review
- Review
- Characteristics and Outcomes of IgA Nephropathy Patients With SGLT2 Inhibitor-Induced Polycythemia.Cureus · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia-inducible factor (HIF)-1α and HIF-2α promote cellular adaptation to acute hypoxia, but during prolonged activation, these isoforms exert mutually antagonistic effects on the redox state and on proinflammatory pathways. Sustained HIF-1α signaling can increase oxidative stress, inflammation, and fibrosis, actions that are opposed by HIF-2α. Imbalances in the interplay between HIF-1α and HIF-2α may contribute to the progression of chronic heart failure, atherosclerotic and hypertensive vascular disorders, and chronic kidney disease. These disorders are characterized by activation of HIF-1α and suppression of HIF-2α, which are potentially related to mitochondrial and peroxisomal dysfunction and suppression of the redox sensor, sirtuin-1. Hypoxia mimetics can potentiate HIF-1α and/or HIF-2α; ideally, such agents should act preferentially to promote HIF-2α while exerting little effect on or acting to suppress HIF-1α. Selective activation of HIF-2α can be achieved with drugs that: 1) inhibit isoform-selective prolyl hydroxylases (e.g., cobalt chloride and roxadustat); or 2) promote the actions of the redox sensor, sirtuin-1 (e.g., sodium-glucose cotransporter 2 inhibitors). Selective HIF-2α signaling through sirtuin-1 activation may explain the effect of sodium-glucose cotransporter 2 inhibitors to simultaneously promote erythrocytosis and ameliorate the development of cardiomyopathy and nephropathy.
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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.