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Albumin Lipidomics Reveals Meaningful Compositional Changes in Advanced Cirrhosis and Its Potential to Promote Inflammation Resolution
Albumin infusions are therapeutically used to revert hypoalbuminemia and to replace the extensively oxidized albumin molecule circulating in patients with acutely decompensated (AD) cirrhosis. Because albumin has high affinity for lipids, here we characterized the albumin lipidome in patients with A...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9134813/ https://www.ncbi.nlm.nih.gov/pubmed/35178899 http://dx.doi.org/10.1002/hep4.1893 |
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author | Casulleras, Mireia Flores‐Costa, Roger Duran‐Güell, Marta Zhang, Ingrid W. López‐Vicario, Cristina Curto, Anna Fernández, Javier Arroyo, Vicente Clària, Joan |
author_facet | Casulleras, Mireia Flores‐Costa, Roger Duran‐Güell, Marta Zhang, Ingrid W. López‐Vicario, Cristina Curto, Anna Fernández, Javier Arroyo, Vicente Clària, Joan |
author_sort | Casulleras, Mireia |
collection | PubMed |
description | Albumin infusions are therapeutically used to revert hypoalbuminemia and to replace the extensively oxidized albumin molecule circulating in patients with acutely decompensated (AD) cirrhosis. Because albumin has high affinity for lipids, here we characterized the albumin lipidome in patients with AD and explored the albumin effects on the release of fatty acid (FA)–derived lipid mediators by peripheral leukocytes. Lipids and lipid mediators were measured by liquid chromatography–tandem mass spectrometry in albumin‐enriched and albumin‐depleted plasma fractions separated by affinity chromatography and in leukocyte incubations from 18 patients with AD and 10 healthy subjects (HS). Lipid mediators were also measured in 41 patients with AD included in an albumin therapy trial. The plasma lipidome associated with AD cirrhosis was characterized by generalized suppression of all lipid classes except FAs. In contrast to HS, albumin from patients with AD had lower content of polyunsaturated FAs (PUFAs), especially of the omega‐3‐PUFA docosahexaenoic acid. Consistent with this, the PUFA‐derived lipid mediator landscape of albumin from patients with AD was dominated by lower content of monohydroxy FA precursors of anti‐inflammatory/pro‐resolving lipid mediators (i.e., 15‐hydroxyeicosatetraenoic acid [15‐HETE]). In addition, albumin from patients with AD was depleted in prostaglandin (PG) E(2), suggesting that this proinflammatory PG primarily travels disassociated to albumin in these patients. Incubation of leukocytes with exogenous albumin reduced PG production while inducing 15‐lipoxygenase expression and 15‐HETE release. Similar effects were seen under lipopolysaccharide plus N‐formylmethionyl‐leucyl‐phenylalanine‐stimulated conditions. Finally, PG levels were lower in patients with AD receiving albumin therapy, whereas 15‐HETE was increased after albumin treatment compared with baseline. Conclusion: Our findings indicate that the albumin lipid composition is severely disorganized in AD cirrhosis and that administration of exogenous albumin has the potential to redirect leukocyte biosynthesis from pro‐inflammatory to pro‐resolving lipid mediators. |
format | Online Article Text |
id | pubmed-9134813 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-91348132022-06-04 Albumin Lipidomics Reveals Meaningful Compositional Changes in Advanced Cirrhosis and Its Potential to Promote Inflammation Resolution Casulleras, Mireia Flores‐Costa, Roger Duran‐Güell, Marta Zhang, Ingrid W. López‐Vicario, Cristina Curto, Anna Fernández, Javier Arroyo, Vicente Clària, Joan Hepatol Commun Original Articles Albumin infusions are therapeutically used to revert hypoalbuminemia and to replace the extensively oxidized albumin molecule circulating in patients with acutely decompensated (AD) cirrhosis. Because albumin has high affinity for lipids, here we characterized the albumin lipidome in patients with AD and explored the albumin effects on the release of fatty acid (FA)–derived lipid mediators by peripheral leukocytes. Lipids and lipid mediators were measured by liquid chromatography–tandem mass spectrometry in albumin‐enriched and albumin‐depleted plasma fractions separated by affinity chromatography and in leukocyte incubations from 18 patients with AD and 10 healthy subjects (HS). Lipid mediators were also measured in 41 patients with AD included in an albumin therapy trial. The plasma lipidome associated with AD cirrhosis was characterized by generalized suppression of all lipid classes except FAs. In contrast to HS, albumin from patients with AD had lower content of polyunsaturated FAs (PUFAs), especially of the omega‐3‐PUFA docosahexaenoic acid. Consistent with this, the PUFA‐derived lipid mediator landscape of albumin from patients with AD was dominated by lower content of monohydroxy FA precursors of anti‐inflammatory/pro‐resolving lipid mediators (i.e., 15‐hydroxyeicosatetraenoic acid [15‐HETE]). In addition, albumin from patients with AD was depleted in prostaglandin (PG) E(2), suggesting that this proinflammatory PG primarily travels disassociated to albumin in these patients. Incubation of leukocytes with exogenous albumin reduced PG production while inducing 15‐lipoxygenase expression and 15‐HETE release. Similar effects were seen under lipopolysaccharide plus N‐formylmethionyl‐leucyl‐phenylalanine‐stimulated conditions. Finally, PG levels were lower in patients with AD receiving albumin therapy, whereas 15‐HETE was increased after albumin treatment compared with baseline. Conclusion: Our findings indicate that the albumin lipid composition is severely disorganized in AD cirrhosis and that administration of exogenous albumin has the potential to redirect leukocyte biosynthesis from pro‐inflammatory to pro‐resolving lipid mediators. John Wiley and Sons Inc. 2022-02-18 /pmc/articles/PMC9134813/ /pubmed/35178899 http://dx.doi.org/10.1002/hep4.1893 Text en © 2022 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Casulleras, Mireia Flores‐Costa, Roger Duran‐Güell, Marta Zhang, Ingrid W. López‐Vicario, Cristina Curto, Anna Fernández, Javier Arroyo, Vicente Clària, Joan Albumin Lipidomics Reveals Meaningful Compositional Changes in Advanced Cirrhosis and Its Potential to Promote Inflammation Resolution |
title | Albumin Lipidomics Reveals Meaningful Compositional Changes in Advanced Cirrhosis and Its Potential to Promote Inflammation Resolution |
title_full | Albumin Lipidomics Reveals Meaningful Compositional Changes in Advanced Cirrhosis and Its Potential to Promote Inflammation Resolution |
title_fullStr | Albumin Lipidomics Reveals Meaningful Compositional Changes in Advanced Cirrhosis and Its Potential to Promote Inflammation Resolution |
title_full_unstemmed | Albumin Lipidomics Reveals Meaningful Compositional Changes in Advanced Cirrhosis and Its Potential to Promote Inflammation Resolution |
title_short | Albumin Lipidomics Reveals Meaningful Compositional Changes in Advanced Cirrhosis and Its Potential to Promote Inflammation Resolution |
title_sort | albumin lipidomics reveals meaningful compositional changes in advanced cirrhosis and its potential to promote inflammation resolution |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9134813/ https://www.ncbi.nlm.nih.gov/pubmed/35178899 http://dx.doi.org/10.1002/hep4.1893 |
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