ArticleProceedings of the National Academy of Sciences of the United States of America2002
Distribution of nitric oxide synthase in normal and cirrhotic human liver.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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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
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 173 citations in OpenAlex.
- Effects of iNOS in Hepatic Warm Ischaemia and Reperfusion Models in Mice and Rats: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2022Pooled it
- Intensive insulin therapy protects the endothelium of critically ill patients.The Journal of clinical investigation · 2005Trial
- A Hepatocyte-to-Stellate Cell Axis Couples Alternate-Day Fasting to Liver Fibrosis Resolution via ATG7 S-Nitrosylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The compartmentalization model of nitrate homeostasis: Role of the salivary glands, skeletal muscle, and liver.EXCLI journal · 2026Review
- Inhibition of hepatic gluconeogenesis in type 2 diabetes by metformin: complementary role of nitric oxide.Medical gas research · 2025Review
- Cirrhotic Cardiomyopathy: Bridging Hepatic and Cardiac Pathophysiology in the Modern Era.Journal of clinical medicine · 2025Review
- Inducible nitric oxide synthase (iNOS): More than an inducible enzyme? Rethinking the classification of NOS isoforms.Pharmacological research · 2025Review
- Article
- Vitamin DExperimental biology and medicine (Maywood, N.J.) · 2025Article
- Selective PPARδ Agonist GW501516 Protects Against LPS-Induced Macrophage Inflammation and Acute Liver Failure in Mice via Suppressing Inflammatory Mediators.Molecules (Basel, Switzerland) · 2024Article
- Endothelial force sensing signals to parenchymal cells to regulate bile and plasma lipids.Science advances · 2024Article
- Albumin, an interesting and functionally diverse protein, varies from 'native' to 'effective' (Review).Molecular medicine reports · 2024Review
- Article
- Effect of the Non-steroidal Anti-inflammatory Drug Diclofenac on Ischemia-Reperfusion Injury in Rat Liver: A Nitric Oxide-Dependent Mechanism.Inflammation · 2023Article
- ASL mRNA-LNP Therapeutic for the Treatment of Argininosuccinic Aciduria Enables Survival Benefit in a Mouse Model.Biomedicines · 2023Article
- Role of Nitric Oxide in Megakaryocyte Function.International journal of molecular sciences · 2023Review
- Selective gene expression profiling contributes to a better understanding of the molecular pathways underlying the histological changes observed after RHMVL.BMC medical genomics · 2022Article
- Cyclic GMP in Liver Cirrhosis-Role in Pathophysiology of Portal Hypertension and Therapeutic Implications.International journal of molecular sciences · 2021Review
- Expression of immunoreactive inducible nitric oxide synthase in pancreatic islet cells from newly diagnosed and long-term type 1 diabetic donors is heterogeneous and not disease-associated.Cell and tissue research · 2021Article
- Four weeks exercise training enhanced the hepatic insulin sensitivity in high fat- and high carbohydrate-diet fed hyperinsulinemic rats.Journal of diabetes and metabolic disorders · 2020Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic liver disorders represent a serious health problem, considering that 300 million people worldwide are hepatitis B virus carriers, and 8,000-10,000 patients per year, in the U.S. alone, die as a result of liver failure caused by hepatitis C infection. Nitric oxide synthase (NOS) regulates hepatic vasculature; however, the patterns of expression and activity of NOS proteins in healthy and diseased human livers are unknown. Sections of diseased (n = 42) and control livers (n = 14) were collected during orthotopic liver transplants and partial hepatectomy. The diseased sections included alcoholic cirrhosis, viral hepatitis, cholestasis, acute necrosis, and uncommon pathologies including alpha(1)-anti-trypsin disorder. The endothelial NOS (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS) were studied by using the citrulline assay, Western immunoblot, immunohistochemistry, and in situ hybridization. The systemic generation of plasma NO metabolites was measured by HPLC. In control livers, Ca(2+)-dependent and -independent NOS activities were identified by Western analysis as eNOS and iNOS, respectively. The eNOS was uniformly distributed in the hepatocytes and also detected in the endothelium of hepatic arteries, terminal hepatic venules, sinusoids, and in biliary epithelium. The iNOS was detected in hepatocytes and localized mainly in the periportal zone of the liver acinus. This pattern of distribution of eNOS and iNOS in normal liver was confirmed by in situ hybridization. In diseased livers, there was a significant increase in Ca(2+)-independent NOS with the corresponding strong appearance of iNOS in the cirrhotic areas. The eNOS was translocated to hepatocyte nuclei. Thus, eNOS and iNOS proteins are differentially expressed in healthy human liver, and this expression is significantly altered in cirrhotic liver disorders.
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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.