ArticleScientific reports2016
Effects of warm ischemia and reperfusion on the liver microcirculatory phenotype of rats: underlying mechanisms and pharmacological therapy.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- Liver sinusoidal endothelial cell fenestrations in metabolic liver disease: from molecular mechanisms to therapeutic perspectives.Cell communication and signaling : CCS · 2026Review
- Simvastatin Alleviates ConA-Induced Autoimmune Hepatitis by Inhibiting CD4Inflammation · 2026Article
- Identification of Wnt/β-catenin- and immune-related genes in hepatic ischemia-reperfusion injury using bulk transcriptomics, single-cell RNA sequencing, and a murine model.Frontiers in immunology · 2026Article
- Recent advances in the role of gasotransmitters in necroptosis.Apoptosis : an international journal on programmed cell death · 2025Review
- Non-coding RNAs: The potential biomarker or therapeutic target in hepatic ischemia-reperfusion injury.World journal of gastroenterology · 2023Review
- Alternative splicing of CEACAM1 by hypoxia-inducible factor-1α enhances tolerance to hepatic ischemia in mice and humans.Science translational medicine · 2023Article
- Novel, Innovative Models to Study Ischemia/Reperfusion-Related Redox Damage in Organ Transplantation.Antioxidants (Basel, Switzerland) · 2022Review
- New progress in understanding roles of nitric oxide during hepatic ischemia-reperfusion injury.World journal of hepatology · 2022Review
- Prevention of Cirrhosis Complications: Looking for Potential Disease Modifying Agents.Journal of clinical medicine · 2021Review
- Automatic Liver Viability Scoring with Deep Learning and Hyperspectral Imaging.Diagnostics (Basel, Switzerland) · 2021Article
- Sitagliptin Modulates Oxidative, Nitrative and Halogenative Stress and Inflammatory Response in Rat Model of Hepatic Ischemia-Reperfusion.Antioxidants (Basel, Switzerland) · 2021Article
- Role of liver sinusoidal endothelial cells in liver diseases.Nature reviews. Gastroenterology & hepatology · 2021Review
- Appropriate timing for hypothermic machine perfusion to preserve livers donated after circulatory death.Molecular medicine reports · 2020Article
- Platelets and Platelet-Derived Extracellular Vesicles in Liver Physiology and Disease.Hepatology communications · 2019Review
- Emricasan Ameliorates Portal Hypertension and Liver Fibrosis in Cirrhotic Rats Through a Hepatocyte-Mediated Paracrine Mechanism.Hepatology communications · 2019Article
- Article
- Resemblance of the human liver sinusoid in a fluidic device with biomedical and pharmaceutical applications.Biotechnology and bioengineering · 2018Article
- Endothelial Dysfunction in Steatotic Human Donor Livers: A Pilot Study of the Underlying Mechanism During Subnormothermic Machine Perfusion.Transplantation direct · 2018Article
- C-C Chemokine Ligand-5 is critical for facilitating macrophage infiltration in the early phase of liver ischemia/reperfusion injury.Scientific reports · 2017Article
- Liraglutide improves liver microvascular dysfunction in cirrhosis: Evidence from translational studies.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Warm ischemia and reperfusion (WIR) causes hepatic damage and may lead to liver failure, however the mechanisms involved are largely unknown. Here we have characterized the microcirculatory status and endothelial phenotype of livers undergoing WIR, and evaluated the use of simvastatin in WIR injury prevention. Male Wistar rats received simvastatin, or vehicle, 30 min before undergoing 60 min of partial warm ischemia (70%) followed by 2 h or 24 h of reperfusion. Hepatic and systemic hemodynamics, liver injury (AST, ALT, LDH), endothelial function (vasodilatation in response to acetylcholine), KLF2 and nitric oxide pathways, oxidative stress, inflammation (neutrophil and macrophage infiltration) and cell death were evaluated. Profound microcirculatory dysfunction occurred rapidly following WIR. This was evidenced by down-regulation of the KLF2 vasoprotective pathway, impaired vasodilatory capability and endothelial activation, altogether leading to increased hepatic vascular resistance and liver inflammation, with significant leukocyte infiltration, oxidative stress and cell death. Simvastatin preserved the hepatic endothelial phenotype, and blunted the detrimental effects of WIR on liver hemodynamics and organ integrity. In conclusion, WIR-induced injury to liver sinusoidal endothelial cells is mitigated by pre-treatment with Simvastatin probably through a KLF2-dependent mechanism.
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