A Novel Immunoassay for Malondialdehyde-Conjugated Low-Density Lipoprotein Measures Dynamic Changes in the Blood of Patients Undergoing Coronary Artery Bypass Graft Surgery

Pandey, Samata; Hartley, Adam; Caga-Anan, Mikhail; Ammari, Tareq; Khan, Ameer; Nguyen, Bao; Kojima, Chiari; Anderson, Jon R.; Lynham, Steven; Johns, Michael; Haskard, Dorian O.; Khamis, Ramzi

doi:10.3390/antiox10081298

Cited by 3 publications

(4 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consequently, there is consumption of the circulating anti-oxLDL antibodies as they beneficially clear the increased antigenic load, forming complexes and trafficking them to the reticuloendothelial system for removal in a homeostatic clearance mechanism. These observations are consistent with other studies from our laboratory, which demonstrate acute reduction in anti-MDA-LDL antibodies following major vascular surgery and coronary artery bypass grafting ( 17 ).…”

Section: Discussionsupporting

confidence: 93%

The Placebo-Controlled Effect of Percutaneous Coronary Intervention on Exercise Induced Changes in Anti-Malondialdehyde-LDL Antibody Levels in Stable Coronary Artery Disease: A Substudy of the ORBITA Trial

Hartley

Shun-Shin

Caga-Anan

et al. 2021

Front. Cardiovasc. Med.

Self Cite

View full text Add to dashboard Cite

Aim: Malondialdehyde-modified low-density lipoprotein (MDA-LDL) forms a significant component of oxidised LDL. The effects of exercise on levels of MDA-LDL and anti-MDA-LDL antibodies are not well-understood. Furthermore, it is not known whether these can be modified in patients with coronary artery disease by percutaneous coronary intervention (PCI).Methods: The Objective Randomised Blinded Investigation with optimal medical Therapy of Angioplasty in stable angina (ORBITA) trial was the first blinded, multi-centre randomised trial of PCI vs. placebo procedure for angina relief. Serum samples were available at four time-points: pre-randomisation pre- (P1) and post- (P2) exercise and post-randomisation (6-weeks following the PCI or placebo procedure), pre- (P3) and post- (P4) exercise. ELISAs were performed using laboratory-developed assays for MDA-LDL (adjusted for Apolipoprotein B) and anti-MDA-LDL antibodies.Results: One hundred ninety-six of the 200 patients (age 66.1 [SD 8.99] years, 28% female) with severe single vessel coronary artery disease suitable for PCI enrolled in the ORBITA trial had blood available for analysis. With exercise at pre-randomisation (P2–P1) there was no significant change in adjusted MDA-LDL (−0.001, 95% CI −0.004 to 0.001; p = 0.287); however, IgG and IgM anti-MDA-LDL significantly declined (−0.022, 95% CI −0.029 to −0.014, p < 0.0001; −0.016, 95% CI −0.024 to −0.008, p = 0.0002, respectively). PCI did not have a significant impact on either the pre-exercise values (P3 controlling for P1) of MDA-LDL (p = 0.102), IgG (p = 0.444) or IgM anti-MDA-LDL (p = 0.909). Nor did PCI impact the exercise induced changes in these markers (P4 controlling for P1, P2, and P3) for MDA-LDL (p = 0.605), IgG (p = 0.725) or IgM anti-MDA-LDL (p = 0.171). Pre-randomisation ischaemia on stress echo did not impact these interactions.Conclusions: Exercise results in an acute reduction in anti-oxLDL antibodies in patients with severe single vessel coronary disease, possibly indicating an induction in homoeostatic clearance via the innate immune system. However, PCI did not ameliorate this effect.

show abstract

Section: Discussionsupporting

confidence: 93%

The Placebo-Controlled Effect of Percutaneous Coronary Intervention on Exercise Induced Changes in Anti-Malondialdehyde-LDL Antibody Levels in Stable Coronary Artery Disease: A Substudy of the ORBITA Trial

Hartley

Shun-Shin

Caga-Anan

et al. 2021

Front. Cardiovasc. Med.

Self Cite

View full text Add to dashboard Cite

show abstract

“…We have recently shown that major cardiac surgery with coronary artery bypass grafting results in a depletion of both IgG and IgM anti-MDA-LDL antibodies in tandem with an increase in MDA-LDL levels [ 18 ]. In other earlier studies, transient increases in plasma oxidized LDL and reduction in plasma anti-MDA-LDL antibodies have been identified following percutaneous coronary intervention, albeit over a shorter time course [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…Sandwich ELISA protocols were established to measure the majority of components within our study. MDA-LDL was measured using LO1 (10 μg/mL) as the capture antibody for MDA-LDL [ 18 ], whilst polyclonal goat anti-human anti-ApoB (Abcam, Cambridge, MA, USA; 1:2000 dilution) was used as the capture antibody for ApoB. A biotinylated anti-ApoB antibody (Abcam, Cambridge, MA, USA; 1:2000), followed by horseradish peroxidase (HRP)-conjugated streptavidin (R&D Systems, Minneapolis, MN, USA; 1:200) were used for detection of both MDA-LDL and ApoB.…”

Section: Methodsmentioning

confidence: 99%

“…We have developed a set of enzyme-linked immunosorbent assays (ELISAs) for measuring MDA-LDL, anti-MDA-LDL antibodies, and MDA-LDL immune complexes, and in this study we have applied them to assess how the humoral immune system is involved in MDA-LDL clearance following the challenge of vascular surgery. We have based our assays for MDA-LDL on monoclonal antibody LO1, an anti-MDA-LDL autoantibody derived from an LDL-receptor deficient mouse [ 18 ]. Using these assays, we have been able to demonstrate reciprocal changes in plasma MDA-LDL and anti-MDA-LDL antibodies, suggesting antibody utilization and depletion in response to surgical stress.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2022

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Cardiac Radiofrequency Ablation Exacerbates Myocardial Injury through Pro-Inflammatory Response and Pro-Oxidative Stress in Elderly Patients with Persistent Atrial Fibrillation

Li,

Zhou,

Guo

et al. 2024

CVP

View full text Add to dashboard Cite

Background: There is a need to assess myocardial damage after radiofrequency ablation of the pulmonary veins (PV) for persistent atrial fibrillation (PAF) in elderly patients. Objective: To evaluate oxidative stress, inflammatory response and myocardial damage in elderly patients with PAF after radiofrequency ablation of the PV. Methods: High-sensitivity troponin T (hsTnT), malondialdehyde-modified low-density lipoprotein (MDA-LDL), acrolein (ACR), lipid hydroperoxide (LHP), toll-like receptor 4 (TLR4), soluble growth stimulation expressed gene 2 (sST2), angiotensin II (Ang II) and myocardial blood flow (MBF) were determined before ablation and at 1, 3 and 5 months after radiofrequency ablation. Results: The levels of hsTnT, MDA-LDL, ACR, LHP, TLR4, sST2 and Ang II were increased 3 months after ablations compared with before ablation and 1 month after ablation, respectively (P<0.001); they were further increased at 5 months after ablation compared with the 1- and 3-month groups, respectively (P<0.001). MBF was decreased in the 3 months group ablations compared with before ablation and 1-month after ablation, respectively (P<0.001), and was further decreased in 5- months after ablations compared with 1-month and 3-month groups, respectively (P<0.001). Patients with epicardial monopolar radiofrequency ablation had higher levels of hsTnT, MDA-LDL, ACR, LHP, TLR4, sST2, Ang II and lower MBF than patients with endocardial monopolar and bipolar radiofrequency ablations, respectively (P<0.001). Conclusion: Monopolar radiofrequency ablation methods could result in more myocardial injury than bipolar radiofrequency ablation. Oxidative stress and inflammatory response may be involved in cardiac radiofrequency ablation-induced myocardial injury, resulting in myocardial ischemia in elderly patients with PAF.

show abstract

A Novel Immunoassay for Malondialdehyde-Conjugated Low-Density Lipoprotein Measures Dynamic Changes in the Blood of Patients Undergoing Coronary Artery Bypass Graft Surgery

Cited by 3 publications

References 22 publications

The Placebo-Controlled Effect of Percutaneous Coronary Intervention on Exercise Induced Changes in Anti-Malondialdehyde-LDL Antibody Levels in Stable Coronary Artery Disease: A Substudy of the ORBITA Trial

The Placebo-Controlled Effect of Percutaneous Coronary Intervention on Exercise Induced Changes in Anti-Malondialdehyde-LDL Antibody Levels in Stable Coronary Artery Disease: A Substudy of the ORBITA Trial

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

Cardiac Radiofrequency Ablation Exacerbates Myocardial Injury through Pro-Inflammatory Response and Pro-Oxidative Stress in Elderly Patients with Persistent Atrial Fibrillation

Contact Info

Product

Resources

About