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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-8868419 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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