ArticleAmerican journal of physiology. Lung cellular and molecular physiology2021
Glucose-6-phosphate dehydrogenase deficiency contributes to metabolic abnormality and pulmonary hypertension.
Article in American journal of physiology. Lung cellular and molecular physiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 2 of them syntheses that pooled it.
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Who cites it
29 citing papers in PubMed, 2 syntheses or guidelines pooled it, 35 citations in OpenAlex.
- Pooled prevalence of Glucose-6-phosphate dehydrogenase deficiency among malaria patients in Ethiopia: a systematic review and meta-analysis.Malaria journal · 2026Pooled it
- Metabolomics in Pulmonary Hypertension-A Useful Tool to Provide Insights into the Dark Side of a Tricky Pathology.International journal of molecular sciences · 2023Pooled it
- NO modulates human airway smooth muscle function by altering glucose-6-phosphate dehydrogenase effects on sGC function in asthma.Redox biology · 2026Article
- The Role of the Pentose Phosphate Pathway in Cardiovascular Diseases.Cardiovascular drugs and therapy · 2026Review
- Hypoxic Pulmonary Hypertension: Molecular Mechanisms and Clinical Research Advances.International journal of molecular sciences · 2026Review
- Myocyte enhancer factor 2A orchestrates vascular redox homeostasis via direct transcriptional activation of SIRT1.Acta biochimica et biophysica Sinica · 2025Article
- Plasma Multiplatform Metabolomics Towards Evaluation of Gender Differences in Pulmonary Arterial Hypertension-A Pilot Study.Biomedicines · 2025Article
- Clinical associations and potential cellular mechanisms linking G6PD deficiency and atherosclerotic cardiovascular disease.npj metabolic health and disease · 2025Review
- Protective effect of apelin-13 in lens epithelial cells via inhibiting oxidative stress-induced apoptosis.BMC ophthalmology · 2024Article
- Metabolic Responses to Redox Stress in Vascular Cells.Antioxidants & redox signaling · 2024Review
- Circulating free heme induces cytokine storm and pulmonary hypertension through the MKK3/p38 axis.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Article
- Metabolomics Meets Clinics: A Multivariate Analysis of Plasma and Urine Metabolic Signatures in Pulmonary Arterial Hypertension.Journal of proteome research · 2024Observational
- GATA2 participates in protection against hypoxia-induced pulmonary vascular remodeling.PloS one · 2024Article
- Clinical challenges in the treatment of a patient with decompensated heart failure and glucose-6-phosphate dehydrogenase deficiency (G6PDd).BMJ case reports · 2023Article
- Plasma untargeted metabolomics with proteinase K discloses phospholipid signature associated with pulmonary arterial hypertension.Scientific reports · 2023Article
- Targeting Mitochondrial Metabolic Dysfunction in Pulmonary Hypertension: Toward New Therapeutic Approaches?International journal of molecular sciences · 2023Review
- Review
- Metabolism, Mitochondrial Dysfunction, and Redox Homeostasis in Pulmonary Hypertension.Antioxidants (Basel, Switzerland) · 2022Review
- Mitochondrial Metabolism, Redox, and Calcium Homeostasis in Pulmonary Arterial Hypertension.Biomedicines · 2022Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
We have previously reported that several patients with idiopathic pulmonary hypertension (PH) had different types of G6PD deficiency. However, the role of G6PD in PH is multifactorial because G6PD is involved in controlling oxidative stress, metabolic switch, and red blood cell fragility. To delineate the contribution of G6PD to PH pathogenesis, we utilized a mouse line with decreased expression of G6PD (10% from wild-type level). We confirmed that mice with G6PD deficiency develop spontaneous pulmonary hypertension with pulmonary artery and right heart remodeling. G6PD deficiency resulted in increased free hemoglobin and activation of the p38 pathway, which we recently reported induces the development of PH in the sugen/hypoxia model via endothelial barrier dysfunction. Metabolomics analysis of G6PD deficient mice indicates the switch to alternative metabolic fluxes that feed into the pentose phosphate pathway (PPP), resulting in the upregulation of oxidative stress, fatty acid pathway, and reduction in pyruvate production. Thus, G6PD deficiency did not reduce PPP flux that is important for proliferation but activated collateral pathways at the cost of increased oxidative stress. Indeed, we found the upregulation of myo-inositol oxidase, reduction in GSH/GSSG ratio, and increased nitration in the lungs of G6PD-deficient mice. Increased oxidative stress also results in the activation of PI3K, ERK1/2, and AMPK that contribute to the proliferation of pulmonary vasculature. Therefore, G6PD deficiency has a multimodal effect, including hemolysis, metabolic reprogramming, and oxidative stress leading to the PH phenotype in mice.
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