ArticleProceedings of the National Academy of Sciences of the United States of America2013
Mutual antagonism between hypoxia-inducible factors 1α and 2α regulates oxygen sensing and cardio-respiratory homeostasis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 42 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
42 citing papers in PubMed, 78 citations in OpenAlex.
- Known pathogenic gene variants and new candidates detected in sudden unexpected infant death using whole genome sequencing.American journal of medical genetics. Part A · 2024Article
- Pericytes contribute to pulmonary vascular remodeling via HIF2α signaling.EMBO reports · 2024Article
- Mutual Regulation between Redox and Hypoxia-Inducible Factors in Cardiovascular and Renal Complications of Diabetes.Antioxidants (Basel, Switzerland) · 2022Review
- Role of the HIF‑1α/SDF‑1/CXCR4 signaling axis in accelerated fracture healing after craniocerebral injury.Molecular medicine reports · 2020Article
- Mutual Antagonism of Hypoxia-Inducible Factor Isoforms in Cardiac, Vascular, and Renal Disorders.JACC. Basic to translational science · 2020Review
- Carotid Body and Metabolic Syndrome: Mechanisms and Potential Therapeutic Targets.International journal of molecular sciences · 2020Review
- Autophagy-dependent and -independent modulation of oxidative and organellar stress in the diabetic heart by glucose-lowering drugs.Cardiovascular diabetology · 2020Review
- Marked and rapid effects of pharmacological HIF-2α antagonism on hypoxic ventilatory control.The Journal of clinical investigation · 2020Article
- Striking parallels between carotid body glomus cell and adrenal chromaffin cell development.Developmental biology · 2018Article
- Nitration of MnSOD in the Carotid Body and Adrenal Gland Induced by Chronic Intermittent Hypoxia.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2018Article
- The role of hypoxia-inducible factors in carotid body (patho) physiology.The Journal of physiology · 2018Review
- Endothelial HIF-2α contributes to severe pulmonary hypertension due to endothelial-to-mesenchymal transition.American journal of physiology. Lung cellular and molecular physiology · 2018Article
- Systems biology of oxygen homeostasis.Wiley interdisciplinary reviews. Systems biology and medicine · 2017Review
- Article
- The role of endothelial HIF-1 αin the response to sublethal hypoxia in C57BL/6 mouse pups.Laboratory investigation; a journal of technical methods and pathology · 2017Article
- Cooperative Oxygen Sensing by the Kidney and Carotid Body in Blood Pressure Control.Frontiers in physiology · 2017Article
- Hypoxia-Inducible Factor Stabilizers: a New Avenue for Reducing BP While Helping Hemoglobin?Current hypertension reports · 2016Review
- Regulation of ventilatory sensitivity and carotid body proliferation in hypoxia by the PHD2/HIF-2 pathway.The Journal of physiology · 2016Article
- Regulation of carotid body oxygen sensing by hypoxia-inducible factors.Pflugers Archiv : European journal of physiology · 2016Review
- Oxygen physiology: sensors and ion channels.Pflugers Archiv : European journal of physiology · 2016Article
Corrections and comments
- Retraction · 2022-09-02Concerns/Issues about Data · Concerns/Issues about Image ·
- Retracted
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Breathing and blood pressure are under constant homeostatic regulation to maintain optimal oxygen delivery to the tissues. Chemosensory reflexes initiated by the carotid body and catecholamine secretion from the adrenal medulla are the principal mechanisms for maintaining respiratory and cardiovascular homeostasis; however, the underlying molecular mechanisms are not known. Here, we report that balanced activity of hypoxia-inducible factor-1 (HIF-1) and HIF-2 is critical for oxygen sensing by the carotid body and adrenal medulla, and for their control of cardio-respiratory function. In Hif2α(+/-) mice, partial HIF-2α deficiency increased levels of HIF-1α and NADPH oxidase 2, leading to an oxidized intracellular redox state, exaggerated hypoxic sensitivity, and cardio-respiratory abnormalities, which were reversed by treatment with a HIF-1α inhibitor or a superoxide anion scavenger. Conversely, in Hif1α(+/-) mice, partial HIF-1α deficiency increased levels of HIF-2α and superoxide dismutase 2, leading to a reduced intracellular redox state, blunted oxygen sensing, and impaired carotid body and ventilatory responses to chronic hypoxia, which were corrected by treatment with a HIF-2α inhibitor. None of the abnormalities observed in Hif1α(+/-) mice or Hif2α(+/-) mice were observed in Hif1α(+/-);Hif2α(+/-) mice. These observations demonstrate that redox balance, which is determined by mutual antagonism between HIF-α isoforms, establishes the set point for hypoxic sensing by the carotid body and adrenal medulla, and is required for maintenance of cardio-respiratory homeostasis.
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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.