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Depletion of Homeostatic Antibodies against Malondialdehyde-Modified Low-Density Lipoprotein Correlates with Adverse Events in Major Vascular Surgery

We aimed to investigate if major vascular surgery induces LDL oxidation, and whether circulating antibodies against malondialdehyde-modified LDL (MDA-LDL) alter dynamically in this setting. We also questioned relationships between these biomarkers and post-operative cardiovascular events. Major surg...

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Autores principales: Hartley, Adam, Pradeep, Magapu, Van den Berg, Victor, Khan, Ameer Hamid Ahmed, Shah, Hasan Ali, Allaf, Mohammed, Chow, Anna, Caga-Anan, Mikhail, Shalhoub, Joseph, Koenig, Wolfgang, Fisher, Michael, Haskard, Dorian O., Khamis, Ramzi Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8868419/
https://www.ncbi.nlm.nih.gov/pubmed/35204154
http://dx.doi.org/10.3390/antiox11020271
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author Hartley, Adam
Pradeep, Magapu
Van den Berg, Victor
Khan, Ameer Hamid Ahmed
Shah, Hasan Ali
Allaf, Mohammed
Chow, Anna
Caga-Anan, Mikhail
Shalhoub, Joseph
Koenig, Wolfgang
Fisher, Michael
Haskard, Dorian O.
Khamis, Ramzi Y.
author_facet Hartley, Adam
Pradeep, Magapu
Van den Berg, Victor
Khan, Ameer Hamid Ahmed
Shah, Hasan Ali
Allaf, Mohammed
Chow, Anna
Caga-Anan, Mikhail
Shalhoub, Joseph
Koenig, Wolfgang
Fisher, Michael
Haskard, Dorian O.
Khamis, Ramzi Y.
author_sort Hartley, Adam
collection PubMed
description We aimed to investigate if major vascular surgery induces LDL oxidation, and whether circulating antibodies against malondialdehyde-modified LDL (MDA-LDL) alter dynamically in this setting. We also questioned relationships between these biomarkers and post-operative cardiovascular events. Major surgery can induce an oxidative stress response. However, the role of the humoral immune system in clearance of oxidized LDL following such an insult is unknown. Plasma samples were obtained from a prospective cohort of 131 patients undergoing major non-cardiac vascular surgery, with samples obtained preoperatively and at 24- and 72 h postoperatively. Enzyme-linked immunoassays were developed to assess MDA-LDL-related antibodies and complexes. Adverse events were myocardial infarction (primary outcome), and a composite of unstable angina, stroke and all-cause mortality (secondary outcome). MDA-LDL significantly increased at 24 h post-operatively (p < 0.0001). Conversely, levels of IgG and IgM anti-MDA-LDL, as well as IgG/IgM-MDA-LDL complexes and total IgG/IgM, were significantly lower at 24 h (each p < 0.0001). A smaller decrease in IgG anti-MDA-LDL related to combined clinical adverse events in a post hoc analysis, withstanding adjustment for age, sex, and total IgG (OR 0.13, 95% CI [0.03–0.5], p < 0.001; p value for trend <0.001). Major vascular surgery resulted in an increase in plasma MDA-LDL, in parallel with a decrease in antibody/complex levels, likely due to antibody binding and subsequent removal from the circulation. Our study provides novel insight into the role of the immune system during the oxidative stress of major surgery, and suggests a homeostatic clearance role for IgG antibodies, with greater reduction relating to downstream adverse events.
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spelling pubmed-88684192022-02-25 Depletion of Homeostatic Antibodies against Malondialdehyde-Modified Low-Density Lipoprotein Correlates with Adverse Events in Major Vascular Surgery Hartley, Adam Pradeep, Magapu Van den Berg, Victor Khan, Ameer Hamid Ahmed Shah, Hasan Ali Allaf, Mohammed Chow, Anna Caga-Anan, Mikhail Shalhoub, Joseph Koenig, Wolfgang Fisher, Michael Haskard, Dorian O. Khamis, Ramzi Y. Antioxidants (Basel) Article We aimed to investigate if major vascular surgery induces LDL oxidation, and whether circulating antibodies against malondialdehyde-modified LDL (MDA-LDL) alter dynamically in this setting. We also questioned relationships between these biomarkers and post-operative cardiovascular events. Major surgery can induce an oxidative stress response. However, the role of the humoral immune system in clearance of oxidized LDL following such an insult is unknown. Plasma samples were obtained from a prospective cohort of 131 patients undergoing major non-cardiac vascular surgery, with samples obtained preoperatively and at 24- and 72 h postoperatively. Enzyme-linked immunoassays were developed to assess MDA-LDL-related antibodies and complexes. Adverse events were myocardial infarction (primary outcome), and a composite of unstable angina, stroke and all-cause mortality (secondary outcome). MDA-LDL significantly increased at 24 h post-operatively (p < 0.0001). Conversely, levels of IgG and IgM anti-MDA-LDL, as well as IgG/IgM-MDA-LDL complexes and total IgG/IgM, were significantly lower at 24 h (each p < 0.0001). A smaller decrease in IgG anti-MDA-LDL related to combined clinical adverse events in a post hoc analysis, withstanding adjustment for age, sex, and total IgG (OR 0.13, 95% CI [0.03–0.5], p < 0.001; p value for trend <0.001). Major vascular surgery resulted in an increase in plasma MDA-LDL, in parallel with a decrease in antibody/complex levels, likely due to antibody binding and subsequent removal from the circulation. Our study provides novel insight into the role of the immune system during the oxidative stress of major surgery, and suggests a homeostatic clearance role for IgG antibodies, with greater reduction relating to downstream adverse events. MDPI 2022-01-29 /pmc/articles/PMC8868419/ /pubmed/35204154 http://dx.doi.org/10.3390/antiox11020271 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hartley, Adam
Pradeep, Magapu
Van den Berg, Victor
Khan, Ameer Hamid Ahmed
Shah, Hasan Ali
Allaf, Mohammed
Chow, Anna
Caga-Anan, Mikhail
Shalhoub, Joseph
Koenig, Wolfgang
Fisher, Michael
Haskard, Dorian O.
Khamis, Ramzi Y.
Depletion of Homeostatic Antibodies against Malondialdehyde-Modified Low-Density Lipoprotein Correlates with Adverse Events in Major Vascular Surgery
title Depletion of Homeostatic Antibodies against Malondialdehyde-Modified Low-Density Lipoprotein Correlates with Adverse Events in Major Vascular Surgery
title_full Depletion of Homeostatic Antibodies against Malondialdehyde-Modified Low-Density Lipoprotein Correlates with Adverse Events in Major Vascular Surgery
title_fullStr Depletion of Homeostatic Antibodies against Malondialdehyde-Modified Low-Density Lipoprotein Correlates with Adverse Events in Major Vascular Surgery
title_full_unstemmed Depletion of Homeostatic Antibodies against Malondialdehyde-Modified Low-Density Lipoprotein Correlates with Adverse Events in Major Vascular Surgery
title_short Depletion of Homeostatic Antibodies against Malondialdehyde-Modified Low-Density Lipoprotein Correlates with Adverse Events in Major Vascular Surgery
title_sort depletion of homeostatic antibodies against malondialdehyde-modified low-density lipoprotein correlates with adverse events in major vascular surgery
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8868419/
https://www.ncbi.nlm.nih.gov/pubmed/35204154
http://dx.doi.org/10.3390/antiox11020271
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