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Depletion of homeostatic antibodies against malondialdehyde-modified low-density lipoprotein correlates with adverse events in major vascular surgery

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Title: Depletion of homeostatic antibodies against malondialdehyde-modified low-density lipoprotein correlates with adverse events in major vascular surgery
Authors: Hartley, A
Pradeep, M
Van den Berg, V
Khan, AHA
Shah, HA
Allaf, M
Chow, A
Caga-Anan, M
Shalhoub, J
Koenig, W
Fisher, M
Haskard, D
Khamis, R
Item Type: Journal Article
Abstract: 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.
Issue Date: 29-Jan-2022
Date of Acceptance: 20-Jan-2022
URI: http://hdl.handle.net/10044/1/94619
DOI: 10.3390/antiox11020271
ISSN: 2076-3921
Publisher: MDPI AG
Journal / Book Title: Antioxidants
Volume: 11
Issue: 2
Copyright Statement: © 2022 by the authors. 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/).
Sponsor/Funder: British Heart Foundation
Wellcome Trust
Funder's Grant Number: FS/17/16/32560
Publication Status: Published
Article Number: ARTN 271
Appears in Collections:Department of Surgery and Cancer
National Heart and Lung Institute
Faculty of Medicine



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