ArticleCardiovascular research2018
Roles for endothelial cell and macrophage Gch1 and tetrahydrobiopterin in atherosclerosis progression.
Article in Cardiovascular research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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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
29 citing papers in PubMed, 46 citations in OpenAlex.
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- Lipoprotein(a) and the Vascular Redox Interface: Linking Arteriosclerosis, Thrombosis, and Vascular Biology.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Association between circulating GTP cyclohydrolase 1 concentrations and acute ischemic stroke: an exploratory case-control study in a Chinese population.Frontiers in neurology · 2026Article
- Nitric Oxide in Biomaterial-Based Therapies for Coronary Heart Disease: Mechanistic Insights, Current Advances, and Translational Prospects.Biomaterials research · 2025Review
- Replicative Endothelial Cell Senescence May Lead to Endothelial Dysfunction by Increasing the BH2/BH4 Ratio Induced by Oxidative Stress, Reducing BH4 Availability, and Decreasing the Expression of eNOS.International journal of molecular sciences · 2024Article
- Cardiomyocyte tetrahydrobiopterin synthesis regulates fatty acid metabolism and susceptibility to ischaemia-reperfusion injury.Experimental physiology · 2023Article
- Proteomics analysis of coronary blood microparticles in patients with acute myocardial infarction.Cardiology journal · 2023Article
- Enhanced external counterpulsation improves dysfunction of forearm muscle caused by radial artery occlusion.Frontiers in cardiovascular medicine · 2023Article
- Comparative transcriptomic and proteomic signature of lung alveolar macrophages reveals the integrin CD11b as a regulatory hub during pneumococcal pneumonia infection.Frontiers in immunology · 2023Article
- Identification of Key Genes and Pathways in Genotoxic Stress Induced Endothelial Dysfunction: Results of Whole Transcriptome Sequencing.Biomedicines · 2022Article
- Sex as a Key Determinant of Peripheral Artery Disease: Epidemiology, Differential Outcomes, and Proposed Biological Mechanisms.The Canadian journal of cardiology · 2022Review
- Agmatine and glycolipid metabolism.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2021Article
- Emerging mechanisms and targeted therapy of ferroptosis in cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- Interplay Between Reactive Oxygen/Reactive Nitrogen Species and Metabolism in Vascular Biology and Disease.Antioxidants & redox signaling · 2021Review
- Protective Effects of Estrogen on Cardiovascular Disease Mediated by Oxidative Stress.Oxidative medicine and cellular longevity · 2021Review
- Ferroptosis and Its Potential Role in Metabolic Diseases: A Curse or Revitalization?Frontiers in cell and developmental biology · 2021Review
- Ligustilide Prevents Radiation Enteritis by Targeting Gch1/BHFrontiers in pharmacology · 2021Article
- Comparative proteomic analysis highlights metabolic dysfunction in α-synucleinopathy.NPJ Parkinson's disease · 2020Article
- Nitric Oxide in Macrophage Immunometabolism: Hiding in Plain Sight.Metabolites · 2020Review
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Authors and funding
10 authors at 1 institution in 2 countries.
Funding
Abstract
Aims: GTP cyclohydrolase I catalyses the first and rate-limiting reaction in the synthesis of tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide synthases (NOS). Both eNOS and iNOS have been implicated in the progression of atherosclerosis, with opposing effects in eNOS and iNOS knockout mice. However, the pathophysiologic requirement for BH4 in regulating both eNOS and iNOS function, and the effects of loss of BH4 on the progression of atherosclerosis remains unknown. Methods and results: Hyperlipidemic mice deficient in Gch1 in endothelial cells and leucocytes were generated by crossing Gch1fl/flTie2cre mice with ApoE-/- mice. Deficiency of Gch1 and BH4 in endothelial cells and myeloid cells was associated with mildly increased blood pressure. High fat feeding for 6 weeks in Gch1fl/flTie2CreApoE-/- mice resulted in significantly decreased circulating BH4 levels, increased atherosclerosis burden and increased plaque macrophage content. Gch1fl/flTie2CreApoE-/- mice showed hallmarks of endothelial cell dysfunction, with increased aortic VCAM-1 expression and decreased endothelial cell dependent vasodilation. Furthermore, loss of BH4 from pro-inflammatory macrophages resulted in increased foam cell formation and altered cellular redox signalling, with decreased expression of antioxidant genes and increased reactive oxygen species. Bone marrow chimeras revealed that loss of Gch1 in both endothelial cells and leucocytes is required to accelerate atherosclerosis. Conclusion: Both endothelial cell and macrophage BH4 play important roles in the regulation of NOS function and cellular redox signalling in atherosclerosis.
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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.