ArticlePulmonary circulation2017
Dysfunctional BMPR2 signaling drives an abnormal endothelial requirement for glutamine in pulmonary arterial hypertension.
Article in Pulmonary circulation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
What it found
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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
56 citing papers in PubMed, 98 citations in OpenAlex.
- First-in-human study assessing safety, tolerability, and pharmacokinetics of 2-hydroxybenzylamine acetate, a selective dicarbonyl electrophile scavenger, in healthy volunteers.BMC pharmacology & toxicology · 2019Trial
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- Roles of Lipid Metabolism in Pulmonary Hypertension: Friend or Foe?Biomolecules · 2025Review
- Rewriting the vascular script: epigenetic modifiers as scribes of metabolic reprogramming in pulmonary hypertension.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Bioenergetics and metabolism of the pulmonary endothelium. Scientific session I: ReSPIRE 2025.American journal of physiology. Lung cellular and molecular physiology · 2025Review
- c-Myc promotes metabolic reprogramming in pulmonary hypertension via the stimulation of glutaminolysis and the reductive tricarboxylic acid cycle.Redox biology · 2025Article
- Associations of Metabolites Related Salt Sensitivity of Blood Pressure and Essential Hypertension in Chinese Population: The EpiSS Study.Nutrients · 2025Article
- Alterations in Mitochondrial Function in Pulmonary Vascular Diseases.Antioxidants & redox signaling · 2025Article
- Article
- Pathophysiology of Group 3 Pulmonary Hypertension Associated with Lung Diseases and/or Hypoxia.International journal of molecular sciences · 2025Review
- Exploring the interplay between mitochondria and endoplasmic reticulum in pulmonary arterial hypertension.Frontiers in cardiovascular medicine · 2025Review
- Article
- Viewing Pulmonary Arterial Hypertension Pathogenesis and Opportunities for Disease-Modifying Therapy Through the Lens of Biomass.JACC. Basic to translational science · 2024Review
- Hypoxia-induced pulmonary hypertension in adults and newborns: implications for drug development.Drug discovery today · 2024Review
- Unveiling the metabolic landscape of pulmonary hypertension: insights from metabolomics.Respiratory research · 2024Review
- Neutrophil extracellular traps promote proliferation of pulmonary smooth muscle cells mediated by CCDC25 in pulmonary arterial hypertension.Respiratory research · 2024Article
- Emerging Epigenetic Targets and Their Molecular Impact on Vascular Remodeling in Pulmonary Hypertension.Cells · 2024Review
- A multimodal approach identifies lactate as a central feature of right ventricular failure that is detectable in human plasma.Frontiers in medicine · 2024Article
- B4 suppresses lymphoma progression by inhibiting fibroblast growth factor binding protein 1 through intrinsic apoptosis.Frontiers in pharmacology · 2024Article
- Inflammation Biomarker Response to Oral 2-Hydroxybenzylamine (2-HOBA) Acetate in Healthy Humans.Inflammation · 2023Article
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 1 country.
Funding
Abstract
Pulmonary arterial hypertension (PAH) is increasingly recognized as a systemic disease driven by alteration in the normal functioning of multiple metabolic pathways affecting all of the major carbon substrates, including amino acids. We found that human pulmonary hypertension patients (WHO Group I, PAH) exhibit systemic and pulmonary-specific alterations in glutamine metabolism, with the diseased pulmonary vasculature taking up significantly more glutamine than that of controls. Using cell culture models and transgenic mice expressing PAH-causing BMPR2 mutations, we found that the pulmonary endothelium in PAH shunts significantly more glutamine carbon into the tricarboxylic acid (TCA) cycle than wild-type endothelium. Increased glutamine metabolism through the TCA cycle is required by the endothelium in PAH to survive, to sustain normal energetics, and to manifest the hyperproliferative phenotype characteristic of disease. The strict requirement for glutamine is driven by loss of sirtuin-3 (SIRT3) activity through covalent modification by reactive products of lipid peroxidation. Using 2-hydroxybenzylamine, a scavenger of reactive lipid peroxidation products, we were able to preserve SIRT3 function, to normalize glutamine metabolism, and to prevent the development of PAH in BMPR2 mutant mice. In PAH, targeting glutamine metabolism and the mechanisms that underlie glutamine-driven metabolic reprogramming represent a viable novel avenue for the development of potentially disease-modifying therapeutics that could be rapidly translated to human studies.
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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.