ArticleAmerican journal of physiology. Heart and circulatory physiology2008
Deficient BH4 production via de novo and salvage pathways regulates NO responses to cytokines in adult cardiac myocytes.
Article in American journal of physiology. Heart and circulatory physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- Endothelial dysfunction due to eNOS uncoupling: molecular mechanisms as potential therapeutic targets.Cellular & molecular biology letters · 2023Article
- Measurement of Tetrahydrobiopterin in Animal Tissue Samples by HPLC with Electrochemical Detection-Protocol Optimization and Pitfalls.Antioxidants (Basel, Switzerland) · 2022Article
- Porphyromonas gingivalis infection alters Nrf2-phase II enzymes and nitric oxide in primary human aortic endothelial cells.Journal of periodontology · 2021Article
- Nutraceutical, Dietary, and Lifestyle Options for Prevention and Treatment of Ventricular Hypertrophy and Heart Failure.International journal of molecular sciences · 2021Review
- Oxidative stress and inflammation contribute to traffic noise-induced vascular and cerebral dysfunction via uncoupling of nitric oxide synthases.Redox biology · 2020Review
- New Therapeutic Implications of Endothelial Nitric Oxide Synthase (eNOS) Function/Dysfunction in Cardiovascular Disease.International journal of molecular sciences · 2019Review
- Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their RegulationPhysiological reviews · 2019Review
- Increasing tetrahydrobiopterin in cardiomyocytes adversely affects cardiac redox state and mitochondrial function independently of changes in NO production.Free radical biology & medicine · 2016Article
- Nitric oxide in liver fibrosis: The role of inducible nitric oxide synthase.Clinical and molecular hepatology · 2015Review
- Comparison of oxygen-induced radical intermediates in iNOS oxygenase domain with those from nNOS and eNOS.Journal of inorganic biochemistry · 2014Article
- Tetrahydrobiopterin in cardiovascular health and disease.Antioxidants & redox signaling · 2014Review
- Nitric oxide synthases in heart failure.Antioxidants & redox signaling · 2013Review
- Synthesis and recycling of tetrahydrobiopterin in endothelial function and vascular disease.Nitric oxide : biology and chemistry · 2011Review
- Cardiac-specific overexpression of GTP cyclohydrolase 1 restores ischaemic preconditioning during hyperglycaemia.Cardiovascular research · 2011Article
- Dihydrofolate reductase protects endothelial nitric oxide synthase from uncoupling in tetrahydrobiopterin deficiency.Free radical biology & medicine · 2011Article
- Regulation of Inducible Nitric Oxide Synthase (iNOS) and its Potential Role in Insulin Resistance, Diabetes and Heart Failure.The open cardiovascular medicine journal · 2011Article
- Cardiac myocyte-specific overexpression of human GTP cyclohydrolase I protects against acute cardiac allograft rejection.American journal of physiology. Heart and circulatory physiology · 2010Article
- Role of tetrahydrobiopterin in resistance to myocardial ischemia in Brown Norway and Dahl S rats.American journal of physiology. Heart and circulatory physiology · 2009Article
- Critical role for tetrahydrobiopterin recycling by dihydrofolate reductase in regulation of endothelial nitric-oxide synthase coupling: relative importance of the de novo biopterin synthesis versus salvage pathways.The Journal of biological chemistry · 2009Article
- Sepiapterin decreases acute rejection and apoptosis in cardiac transplants independently of changes in nitric oxide and inducible nitric-oxide synthase dimerization.The Journal of pharmacology and experimental therapeutics · 2009Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Adult rat cardiac myocytes typically display a phenotypic response to cytokines manifested by low or no increases in nitric oxide (NO) production via inducible NO synthase (iNOS) that distinguishes them from other cell types. To better characterize this response, we examined the expression of tetrahydrobiopterin (BH4)-synthesizing and arginine-utilizing genes in cytokine-stimulated adult cardiac myocytes. Intracellular BH4 and 7,8-dihydrobiopterin (BH2) and NO production were quantified. Cytokines induced GTP cyclohydrolase and its feedback regulatory protein but with deficient levels of BH4 synthesis. Despite the induction of iNOS protein, cytokine-stimulated adult cardiac myocytes produced little or no increase in NO versus unstimulated cells. Western blot analysis under nonreducing conditions revealed the presence of iNOS monomers. Supplementation with sepiapterin (a precursor of BH4) increased BH4 as well as BH2, but this did not enhance NO levels or eliminate iNOS monomers. Similar findings were confirmed in vivo after treatment of rat cardiac allograft recipients with sepiapterin. It was found that expression of dihydrofolate reductase, required for full activity of the salvage pathway, was not detected in adult cardiac myocytes. Thus, adult cardiac myocytes have a limited capacity to synthesize BH4 after cytokine stimulation. The mechanisms involve posttranslational factors impairing de novo and salvage pathways. These conditions are unable to support active iNOS protein dimers necessary for NO production. These findings raise significant new questions about the prevailing understanding of how cytokines, via iNOS, cause cardiac dysfunction and injury in vivo during cardiac inflammatory disease states since cardiac myocytes are not a major source of high NO production.
Indexed as
Identifiers
What OpenQuestion holds
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.