ArticleCritical care (London, England)2015
Experimental acute lung injury induces multi-organ epigenetic modifications in key angiogenic genes implicated in sepsis-associated endothelial dysfunction.
Article in Critical care (London, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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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
36 citing papers in PubMed, 61 citations in OpenAlex.
- Epigenetic reprogramming by BCG (Bacillus Calmette-Guérin) vaccination: A novel strategy to reverse immunodeficiency in chronic kidney disease.The Indian journal of medical research · 2026Review
- Diffuse alveolar damage, acute respiratory distress syndrome (ARDS), and non-cardiogenic pulmonary edema. Part 1: ARDS endotypes, including systemic inflammatory response syndrome and sepsis, with dog and cat examples.Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc · 2026Review
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- Emerging Roles and Possible Therapeutic Applications of Arachidonic Acid Metabolites in Sepsis and Sepsis-Associated Organ Dysfunction.Drug design, development and therapy · 2026Review
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- Epigenetic mechanisms mediate cytochrome P450 1A1 expression and lung endothelial injury caused by MRSA in vitro and in vivo.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Identification of m5C-Related gene diagnostic biomarkers for sepsis: a machine learning study.Frontiers in genetics · 2024Article
- CryoGrid-PIXUL-RNA: high throughput RNA isolation platform for tissue transcript analysis.BMC genomics · 2023Article
- ADAM10-a "multitasker" in sepsis: focus on its posttranslational target.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- Advances in the Study of Immunosuppressive Mechanisms in Sepsis.Journal of inflammation research · 2023Review
- MICROVASCULAR ENDOTHELIAL ACTIVATION/DYSFUNCTION AND DYSREGULATION OF THE ANGIOPOIETIN-TIE2 SYSTEM IN THE PATHOGENESIS OF LIFE-THREATENING INFECTIONS.Transactions of the American Clinical and Climatological Association · 2023Article
- Acute respiratory distress syndrome heterogeneity and the septic ARDS subgroup.Frontiers in immunology · 2023Review
- Organotypic heterogeneity in microvascular endothelial cell responses in sepsis-a molecular treasure trove and pharmacological Gordian knot.Frontiers in medicine · 2023Review
- Acute lung injury caused by sepsis: how does it happen?Frontiers in medicine · 2023Review
- Renal microvascular endothelial cell responses in sepsis-induced acute kidney injury.Nature reviews. Nephrology · 2022Review
- Traumatized triad of complementopathy, endotheliopathy, and coagulopathy - Impact on clinical outcomes in severe polytrauma patients.Frontiers in immunology · 2022Article
- Role of serum albumin and proteinuria in patients with SARS-CoV-2 pneumonia.International journal of clinical practice · 2021Article
- Angiogenesis: A Cellular Response to Traumatic Injury.Shock (Augusta, Ga.) · 2021Review
- Emerging therapeutic targets for sepsis.Expert opinion on therapeutic targets · 2021Review
- Epigenetic Regulation in Sepsis, Role in Pathophysiology and Therapeutic Perspective.Frontiers in medicine · 2021Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
introductionThe Tie2/angiopoietin (Tie2/Ang) and vascular endothelial growth factor receptor-ligand systems (VEGFR/VEGF) are recognized to play important roles in the regulation of microvascular endothelial function. Downregulation of these genes during sepsis has been implicated in the pathogenesis of sepsis-related microvascular leak and multiple organ dysfunction syndrome. Mechanisms responsible for dysregulation of angiogenic genes in sepsis are poorly defined.
methodsWestern blot, reverse transcription-polymerase chain reaction, and multiplex chromatin immunoprecipitation platform (Matrix ChIP) were used to investigate serum albumin leak, changes in gene expression, and associated epigenetic alterations in a murine model of acute lung injury-induced sepsis (ALI-sepsis).
resultsExperimental ALI-sepsis induced microvascular leak and downregulation of expression of Angpt1 (Ang1), Tek (Tie2), and Kdr (Vegfr2 or Flk-1) genes in the lung, kidney, and liver. These changes correlate with a decrease in RNA polymerase II density at these genes, and the greatest response was observed in the lung. ALI-sepsis reduced levels of transcription-permissive histone H3 lysine acetylation (H3KAc) at these loci in all examined tissues. Decreases in permissive H3K4m3 and H3Km2 marks were detected only in the lung. In contrast, only minimal alterations in transcription-repressive histone modifications (H3K27m3, H3K9m2, H3K9m3, and H4K20m3) were observed in all tissues.
conclusionsOur results demonstrate that decreases in transcription-permissive, but not increases in transcription-repressive, histone modifications at Angpt1, Tek, and Kdr are a systemic, rather than a lung-restricted, response, involving key end-organs in experimental ALI-sepsis. Given that ventilator-associated pneumonia is a major cause of sepsis in critically ill patients, elucidation of mechanisms mediating epigenetic alterations during sepsis provides fundamental new insights into the pathogenesis of sepsis-induced microvascular leak and subsequent end-organ injury/dysfunction.
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