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

Adam Hartley, Magapu Pradeep, Victor Van den Berg, Ameer Hamid Ahmed Khan, Hasan Ali Shah, Mohammed Allaf, Anna Chow, Mikhail Caga-Anan, Joseph Shalhoub, Wolfgang Koenig, Michael Fisher, Dorian O. Haskard, Ramzi Y. Khamis*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)
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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.

Original languageEnglish
Article number271
Issue number2
Publication statusPublished - 29 Jan 2022

Bibliographical note

Funding Information:
Funding: This work was supported by the National Institute for Health Research Imperial College London Biomedical Research Centre. RK is funded by a British Heart Foundation (BHF) Clinical Research Fellowship (FS/17/16/32560). DH received professorial chair funding from the BHF. AH is funded by a Wellcome Trust Clinical Research Fellowship (220572/Z/20/Z). We also acknowledge funding from the Raissa and Anton Sansour Fund at Imperial Healthcare Charity.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.


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