ArticleFree radical biology & medicine2011
Modeling of biopterin-dependent pathways of eNOS for nitric oxide and superoxide production.
Article in Free radical biology & medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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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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.
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Who cites it
16 citing papers in PubMed, 42 citations in OpenAlex.
- Mitochondria-associated endoplasmic reticulum membranes: Emerging regulators of cardiac microvascular ischemia/reperfusion injury (Review).International journal of molecular medicine · 2026Review
- Nanoparticle Drug Delivery Systems for Atherosclerosis: Precision Targeting, Inflammatory Modulation, and Plaque Stabilization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- The role and mechanisms of microvascular damage in the ischemic myocardium.Cellular and molecular life sciences : CMLS · 2023Review
- Systems biology of angiogenesis signaling: Computational models and omics.WIREs mechanisms of disease · 2022Review
- Empagliflozin attenuates cardiac microvascular ischemia/reperfusion injury through improving mitochondrial homeostasis.Cardiovascular diabetology · 2022Article
- Circuits Regulating Superoxide and Nitric Oxide Production and Neutralization in Different Cell Types: Expression of Participating Genes and Changes Induced by Ionizing Radiation.Antioxidants (Basel, Switzerland) · 2020Article
- Endothelial dysfunction and myocardial injury after major emergency abdominal surgery: a prospective cohort study.BMC anesthesiology · 2020Article
- Aerobic Exercises Induce Antioxidant Pathways Activation in Rats.International journal of preventive medicine · 2020Article
- Roles of phosphodiesterases in the regulation of the cardiac cyclic nucleotide cross-talk signaling network.Journal of molecular and cellular cardiology · 2016Article
- Understanding the Causes and Implications of Endothelial Metabolic Variation in Cardiovascular Disease through Genome-Scale Metabolic Modeling.Frontiers in cardiovascular medicine · 2016Review
- New horizons in pulmonary arterial hypertension therapies.European respiratory review : an official journal of the European Respiratory Society · 2013Review
- Hyperglycemia induces differential change in oxidative stress at gene expression and functional levels in HUVEC and HMVEC.Cardiovascular diabetology · 2013Article
- Endothelial NO and O₂·⁻ production rates differentially regulate oxidative, nitroxidative, and nitrosative stress in the microcirculation.Free radical biology & medicine · 2013Article
- Nitric oxide synthases in heart failure.Antioxidants & redox signaling · 2013Review
- A kinetic platform to determine the fate of nitric oxide in Escherichia coli.PLoS computational biology · 2013Article
- Local oxidative and nitrosative stress increases in the microcirculation during leukocytes-endothelial cell interactions.PloS one · 2012Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Endothelial dysfunction is associated with increase in oxidative stress and low NO bioavailability. The endothelial NO synthase (eNOS) uncoupling is considered an important factor in endothelial cell oxidative stress. Under increased oxidative stress, the eNOS cofactor tetrahydrobiopterin (BH(4)) is oxidized to dihydrobiopterin, which competes with BH(4) for binding to eNOS, resulting in eNOS uncoupling and reduction in NO production. The importance of the ratio of BH(4) to oxidized biopterins versus absolute levels of total biopterin in determining the extent of eNOS uncoupling remains to be determined. We have developed a computational model to simulate the kinetics of the biochemical pathways of eNOS for both NO and O(2)(•-) production to understand the roles of BH(4) availability and total biopterin (TBP) concentration in eNOS uncoupling. The downstream reactions of NO, O(2)(•-), ONOO(-), O(2), CO(2), and BH(4) were also modeled. The model predicted that a lower [BH(4)]/[TBP] ratio decreased NO production but increased O(2)(•-) production from eNOS. The NO and O(2)(•-) production rates were independent above 1.5μM [TBP]. The results indicate that eNOS uncoupling is a result of a decrease in [BH(4)]/[TBP] ratio, and a supplementation of BH(4) might be effective only when the [BH(4)]/[TBP] ratio increases. The results from this study will help us understand the mechanism of endothelial dysfunction.
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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.