ArticleJournal of clinical medicine2020
Inhibition of Anaplerosis Attenuated Vascular Proliferation in Pulmonary Arterial Hypertension.
Article in Journal of clinical medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- Hyperuricemia and Hypoxic Pulmonary Hypertension: Pathogenic Links, Clinical Evidence, and Emerging Therapeutic Insights.Cardiovascular drugs and therapy · 2026Review
- Poly-Pharmacologic Disruption of the Proliferative-to-Mesenchymal Fate Branch Point Reverses EndMT and Pulmonary Hypertension.Research square · 2026Article
- Pathogenesis of Pulmonary Artery Remodeling: TGF-Beta Signaling and Inhibin Subunit Beta A in Group 1 and 2 Pulmonary Hypertension.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- The Critical Role of HMGB1Cys106 in Regulating Sex-Specific p53 Signaling in Pulmonary Arterial Hypertension.American journal of respiratory cell and molecular biology · 2025Article
- Neutrophil-Endothelium Interaction Mediated by S100A9 Promotes Pulmonary Vascular Remodeling During Pulmonary Hypertension.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Endothelial PHD2 deficiency induces apoptosis resistance and inflammation via AKT activation and AIP1 loss independent of HIF2α.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Study on the mechanism of echinacoside in preventing and treating hypoxic pulmonary hypertension based on proteomic analyses.Pharmacology research & perspectives · 2024Article
- Targeting Mitochondrial Metabolic Dysfunction in Pulmonary Hypertension: Toward New Therapeutic Approaches?International journal of molecular sciences · 2023Review
- Akt-Dependent Glycolysis-Driven Lipogenesis Supports Proliferation and Survival of Human Pulmonary Arterial Smooth Muscle Cells in Pulmonary Hypertension.Frontiers in medicine · 2022Article
- Sex Dimorphism in Pulmonary Hypertension: The Role of the Sex Chromosomes.Antioxidants (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Vascular remodeling is considered a key event in the pathogenesis of pulmonary arterial hypertension (PAH). However, mechanisms of gaining the proliferative phenotype by pulmonary vascular cells are still unresolved. Due to well-established pyruvate dehydrogenase (PDH) deficiency in PAH pathogenesis, we hypothesized that the activation of another branch of pyruvate metabolism, anaplerosis, via pyruvate carboxylase (PC) could be a key contributor to the metabolic reprogramming of the vasculature. In sugen/hypoxic PAH rats, vascular proliferation was found to be accompanied by increased activation of Akt signaling, which upregulated membrane Glut4 translocation and caused upregulation of hexokinase and pyruvate kinase-2, and an overall increase in the glycolytic flux. Decreased PDH activity and upregulation of PC shuttled more pyruvate to oxaloacetate. This results in the anaplerotic reprogramming of lung vascular cells and their subsequent proliferation. Treatment of sugen/hypoxia rats with the PC inhibitor, phenylacetic acid 20 mg/kg, starting after one week from disease induction, significantly attenuated right ventricular systolic pressure, Fulton index, and pulmonary vascular cell proliferation. PC inhibition reduced the glycolytic shift by attenuating Akt-signaling, glycolysis, and restored mitochondrial pyruvate oxidation. Our findings suggest that targeting PC mediated anaplerosis is a potential therapeutic intervention for the resolution of vascular remodeling in PAH.
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Registered trials
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