ArticleEuropean heart journal2023
Purine synthesis suppression reduces the development and progression of pulmonary hypertension in rodent models.
Article in European heart journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- AdipocyteCells · 2026Article
- Snhg18 promotes hypoxic pulmonary hypertension by enhancing glycolysis.Respiratory research · 2026Article
- Purine metabolic adaptation protects the endothelium from disturbed flow-induced DNA damage and atherosclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Advances in the pathogenesis and clinical management of pulmonary hypertension.Medical review (2021) · 2026Review
- 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
- Integrated multi-omics analysis of dampness-heat gout reveals diagnostic biomarkers and therapeutic targets.Frontiers in immunology · 2026Article
- Metabolic functions for molecular chaperones and stress proteins in microcephaly.Cellular and molecular life sciences : CMLS · 2025Review
- Reprogrammed glucose metabolism in vascular smooth muscle cells and its implications for vascular diseases.Pharmacological research · 2025Review
- c-Myc promotes metabolic reprogramming in pulmonary hypertension via the stimulation of glutaminolysis and the reductive tricarboxylic acid cycle.Redox biology · 2025Article
- C-type natriuretic peptide attenuates enhanced glycolysis and de novo pyrimidine synthesis in pericytes of patients with pulmonary arterial hypertension.Communications biology · 2025Article
- Increased Generation of Hypoxanthine: How Adaptation of Purine Metabolism Drives Vascular Remodeling in Pulmonary Hypertension.JACC. Basic to translational science · 2025Article
- Hypoxanthine Promotes Pulmonary Vascular Remodeling and Adenosine Deaminase Is a Therapeutic Target for Pulmonary Hypertension.JACC. Basic to translational science · 2025Article
- Single Test-Based Diagnosis and Subtyping of Pulmonary Hypertension Caused by Fibrosing Mediastinitis Using Plasma Metabolic Analysis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Mendelian randomization study of serum uric acid levels and urate-lowering drugs on pulmonary arterial hypertension outcomes.Scientific reports · 2025Article
- Discrepancies between human and murine model cerebral aneurysms at single-cell resolution.Frontiers in cell and developmental biology · 2025Article
- Identification of potential biomarkers and pathways involved in high-altitude pulmonary edema using GC-MS and LC-MS metabolomic methods.Scientific reports · 2024Article
- 5-Aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase promotes pulmonary arterial smooth muscle cell proliferation via the Ras signaling pathway.American journal of physiology. Cell physiology · 2024Article
- Exploring the anticancer mechanism of cardiac glycosides using proteome integral solubility alteration approach.Cancer medicine · 2024Article
- Lactate dehydrogenase A (LDHA)-mediated lactate generation promotes pulmonary vascular remodeling in pulmonary hypertension.Journal of translational medicine · 2024Article
- Peritoneal Infusion of Oxygen Microbubbles Alters the Metabolomic Profile of the Lung and Spleen in Acute Hypoxic Exposure.Bioengineering (Basel, Switzerland) · 2024Article
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Authors and funding
25 authors at 6 institutions in 2 countries.
Funding
Abstract
aimsProliferation of vascular smooth muscle cells (VSMCs) is a hallmark of pulmonary hypertension (PH). Proliferative cells utilize purine bases from the de novo purine synthesis (DNPS) pathways for nucleotide synthesis; however, it is unclear whether DNPS plays a critical role in VSMC proliferation during development of PH. The last two steps of DNPS are catalysed by the enzyme 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase (ATIC). This study investigated whether ATIC-driven DNPS affects the proliferation of pulmonary artery smooth muscle cells (PASMCs) and the development of PH. METHODS AND
resultsMetabolites of DNPS in proliferative PASMCs were measured by liquid chromatography-tandem mass spectrometry. ATIC expression was assessed in platelet-derived growth factor-treated PASMCs and in the lungs of PH rodents and patients with pulmonary arterial hypertension. Mice with global and VSMC-specific knockout of Atic were utilized to investigate the role of ATIC in both hypoxia- and lung interleukin-6/hypoxia-induced murine PH. ATIC-mediated DNPS at the mRNA, protein, and enzymatic activity levels were increased in platelet-derived growth factor-treated PASMCs or PASMCs from PH rodents and patients with pulmonary arterial hypertension. In cultured PASMCs, ATIC knockdown decreased DNPS and nucleic acid DNA/RNA synthesis, and reduced cell proliferation. Global or VSMC-specific knockout of Atic attenuated vascular remodelling and inhibited the development and progression of both hypoxia- and lung IL-6/hypoxia-induced PH in mice.
conclusionTargeting ATIC-mediated DNPS compromises the availability of purine nucleotides for incorporation into DNA/RNA, reducing PASMC proliferation and pulmonary vascular remodelling and ameliorating the development and progression of PH.
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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 Socratic graph.