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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| Format: | Article |
| Language: | English |
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MDPI AG
2022-01-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/2/271 |
| _version_ | 1797483284703215616 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Adam Hartley |
| collection | DOAJ |
| 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 (<i>p</i> < 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 <i>p</i> < 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], <i>p</i> < 0.001; <i>p</i> 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. |
| first_indexed | 2024-03-09T22:44:47Z |
| format | Article |
| id | doaj.art-aed2cec147c54aa8939585f8e494a9be |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T22:44:47Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-aed2cec147c54aa8939585f8e494a9be2023-11-23T18:31:07ZengMDPI AGAntioxidants2076-39212022-01-0111227110.3390/antiox11020271Depletion of Homeostatic Antibodies against Malondialdehyde-Modified Low-Density Lipoprotein Correlates with Adverse Events in Major Vascular SurgeryAdam Hartley0Magapu Pradeep1Victor Van den Berg2Ameer Hamid Ahmed Khan3Hasan Ali Shah4Mohammed Allaf5Anna Chow6Mikhail Caga-Anan7Joseph Shalhoub8Wolfgang Koenig9Michael Fisher10Dorian O. Haskard11Ramzi Y. Khamis12National Heart and Lung Institute, Imperial College London, London W12 0NN, UKLiverpool Heart and Chest Hospital, Liverpool L14 3PE, UKDepartment of Cardiology, Erasmus Medical Centre, University Medical Center Rotterdam, 3015 GD Rotterdam, The NetherlandsDepartment of Medicine, Imperial College London, London SW7 2AZ, UKDepartment of Medicine, Imperial College London, London SW7 2AZ, UKDepartment of Medicine, Imperial College London, London SW7 2AZ, UKDepartment of Medicine, Imperial College London, London SW7 2AZ, UKNational Heart and Lung Institute, Imperial College London, London W12 0NN, UKAcademic 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, UKDeutsches Herzzentrum München, Technische Universität München, Munich, Germany and DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Lazarettstraße 36, 80636 Munich, GermanyInstitute for Cardiovascular Medicine and Science, Liverpool Heart and Chest Hospital NHS Trust and Royal Liverpool and Broadgreen NHS Trust, Liverpool L14 3PE, UKNational Heart and Lung Institute, Imperial College London, London W12 0NN, UKNational Heart and Lung Institute, Imperial College London, London W12 0NN, UKWe 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 (<i>p</i> < 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 <i>p</i> < 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], <i>p</i> < 0.001; <i>p</i> 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.https://www.mdpi.com/2076-3921/11/2/271atherosclerosislow-density lipoprotein (LDL)oxidized LDLcomplementanti-oxidized LDL antibodiesimmune complex |
| spellingShingle | 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 Depletion of Homeostatic Antibodies against Malondialdehyde-Modified Low-Density Lipoprotein Correlates with Adverse Events in Major Vascular Surgery Antioxidants atherosclerosis low-density lipoprotein (LDL) oxidized LDL complement anti-oxidized LDL antibodies immune complex |
| 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 | atherosclerosis low-density lipoprotein (LDL) oxidized LDL complement anti-oxidized LDL antibodies immune complex |
| url | https://www.mdpi.com/2076-3921/11/2/271 |
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