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Article

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

1
National Heart and Lung Institute, Imperial College London, London W12 0NN, UK
2
Liverpool Heart and Chest Hospital, Liverpool L14 3PE, UK
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Department of Cardiology, Erasmus Medical Centre, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands
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Department of Medicine, Imperial College London, London SW7 2AZ, UK
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Academic Section of Vascular Surgery, Department of Surgery & Cancer, Imperial College London, London, UK and Imperial Vascular Unit, Imperial College Healthcare NHS Trust, London W2 1NY, UK
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Deutsches Herzzentrum München, Technische Universität München, Munich, Germany and DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Lazarettstraße 36, 80636 Munich, Germany
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Institute for Cardiovascular Medicine and Science, Liverpool Heart and Chest Hospital NHS Trust and Royal Liverpool and Broadgreen NHS Trust, Liverpool L14 3PE, UK
*
Author to whom correspondence should be addressed.
Academic Editor: Stanley Omaye
Antioxidants 2022, 11(2), 271; https://doi.org/10.3390/antiox11020271
Received: 17 November 2021 / Revised: 6 January 2022 / Accepted: 20 January 2022 / Published: 29 January 2022
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. View Full-Text
Keywords: atherosclerosis; low-density lipoprotein (LDL); oxidized LDL; complement; anti-oxidized LDL antibodies; immune complex atherosclerosis; low-density lipoprotein (LDL); oxidized LDL; complement; anti-oxidized LDL antibodies; immune complex
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MDPI and ACS Style

Hartley, A.; Pradeep, M.; Van den Berg, V.; Khan, A.H.A.; Shah, H.A.; Allaf, M.; Chow, A.; Caga-Anan, M.; Shalhoub, J.; Koenig, W.; Fisher, M.; Haskard, D.O.; Khamis, R.Y. Depletion of Homeostatic Antibodies against Malondialdehyde-Modified Low-Density Lipoprotein Correlates with Adverse Events in Major Vascular Surgery. Antioxidants 2022, 11, 271. https://doi.org/10.3390/antiox11020271

AMA Style

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 DO, Khamis RY. Depletion of Homeostatic Antibodies against Malondialdehyde-Modified Low-Density Lipoprotein Correlates with Adverse Events in Major Vascular Surgery. Antioxidants. 2022; 11(2):271. https://doi.org/10.3390/antiox11020271

Chicago/Turabian Style

Hartley, Adam, Magapu Pradeep, Victor Van den Berg, Ameer H.A. Khan, Hasan A. Shah, Mohammed Allaf, Anna Chow, Mikhail Caga-Anan, Joseph Shalhoub, Wolfgang Koenig, Michael Fisher, Dorian O. Haskard, and Ramzi Y. Khamis. 2022. "Depletion of Homeostatic Antibodies against Malondialdehyde-Modified Low-Density Lipoprotein Correlates with Adverse Events in Major Vascular Surgery" Antioxidants 11, no. 2: 271. https://doi.org/10.3390/antiox11020271

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