ArticleAmerican journal of respiratory and critical care medicine2016
Mechanisms of Lipid Accumulation in the Bone Morphogenetic Protein Receptor Type 2 Mutant Right Ventricle.
Article in American journal of respiratory and critical care medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 2 of them syntheses that pooled it.
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Who cites it
72 citing papers in PubMed, 2 syntheses or guidelines pooled it, 105 citations in OpenAlex.
- 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
- Metabolic Remodeling in the Pressure-Loaded Right Ventricle: Shifts in Glucose and Fatty Acid Metabolism-A Systematic Review and Meta-Analysis.Journal of the American Heart Association · 2019Pooled it
- Mechanistic Phase II Clinical Trial of Metformin in Pulmonary Arterial Hypertension.Journal of the American Heart Association · 2020Trial
- Impact of Lipid Profile Alterations on the Right Heart Function and Prognosis in Pre-Capillary Pulmonary Hypertension Patients: A Prospective Cohort Study.Respirology (Carlton, Vic.) · 2026Article
- Mitochondrial arginase 2 regulates hematopoietic and cardiovascular adaptation to hypoxia.Blood vessels, thrombosis & hemostasis · 2026Article
- Case Report: Pulmonary artery biopsy findings in a patient with a BMPR2 variant-associated pulmonary arterial hypertension.Frontiers in medicine · 2026Article
- Beta-Alanine Supplementation Ameliorates Right Ventricular Remodeling Caused by Monocrotaline-Induced Pulmonary Hypertension.Pulmonary circulation · 2026Article
- 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
- TSH promotes right ventricle hypertrophy and energy metabolism remodeling in PAH mice.Endocrine connections · 2025Article
- Plasma non-targeted metabolomics unravels the metabolic features of normal trans-right heart.Metabolomics : Official journal of the Metabolomic Society · 2025Article
- Inhibiting CD36 palmitoylation improves cardiac function post-infarction by regulating lipid metabolic homeostasis and autophagy.Nature communications · 2025Article
- Lipid Ratios for Diagnosis and Prognosis of Pulmonary Hypertension.American journal of respiratory and critical care medicine · 2025Article
- Metabolic alterations in human pulmonary artery smooth muscle cells treated with PDGF-BB.Animal models and experimental medicine · 2025Article
- Multi-omics analysis of two rat models reveals potential role of vesicle transport and autophagy in right ventricular remodeling.Scientific reports · 2025Article
- Transcriptional Signatures of the Right Ventricle in End-Stage Heart Failure.Pulmonary circulation · 2025Article
- Mechanisms and treatment of pulmonary arterial hypertension.Nature reviews. Cardiology · 2025Review
- Deep phenotyping of unaffected carriers of pathogenicThe European respiratory journal · 2024Article
- Pathophysiology of the right ventricle and its pulmonary vascular interaction.The European respiratory journal · 2024Review
- Carnitine consumption and effect of oral supplementation in human pulmonary arterial hypertension: A pilot study.Pulmonary circulation · 2024Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
Abstract
rationaleIn heritable pulmonary arterial hypertension with germline mutation in the bone morphogenetic protein receptor type 2 (BMPR2) gene, right ventricle (RV) dysfunction is associated with RV lipotoxicity; however, the underlying mechanism for lipid accumulation is not known.
objectivesWe hypothesized that lipid accumulation in cardiomyocytes with BMPR2 mutation occurs owing to alterations in lipid transport and impaired fatty acid oxidation (FAO), which is exacerbated by a high-lipid (Western) diet (WD).
methodsWe used a transgenic mouse model of pulmonary arterial hypertension with mutant BMPR2 and generated a cardiomyocyte cell line with BMPR2 mutation. Electron microscopy and metabolomic analysis were performed on mouse RVs. MEASUREMENTS AND MAIN
resultsBy metabolomics analysis, we found an increase in long-chain fatty acids in BMPR2 mutant mouse RVs compared with controls, which correlated with cardiac index. BMPR2-mutant cardiomyocytes had increased lipid compared with controls. Direct measurement of FAO in the WD-fed BMPR2-mutant RV showed impaired palmitate-linked oxygen consumption, and metabolomics analysis showed reduced indices of FAO. Using both mutant BMPR2 mouse RVs and cardiomyocytes, we found an increase in the uptake of (14)C-palmitate and fatty acid transporter CD36 that was further exacerbated by WD.
conclusionsTaken together, our data suggest that impaired FAO and increased expression of the lipid transporter CD36 are key mechanisms underlying lipid deposition in the BMPR2-mutant RV, which are exacerbated in the presence of dietary lipids. These findings suggest important features leading to RV lipotoxicity in pulmonary arterial hypertension and may point to novel areas of therapeutic intervention.
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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.