Acute and long-term effect of percutaneous coronary intervention on serially-measured oxidative, inflammatory, and coagulation biomarkers in patients with stable angina

Abstract

Objectives To derive insights into the temporal changes in oxidative, inflammatory and coagulation biomarkers in patients with stable angina undergoing percutaneous coronary intervention (PCI). Background PCI is associated with a variety of biochemical and mechanical stresses to the vessel wall. Oxidized phospholipids are present on plasminogen (OxPL-PLG) and potentiate fibrinolysis in vitro. We recently showed that OxPL-PLG increase following acute myocardial infarction, suggesting that they are involved in atherothrombosis. Methods Plasma samples were collected before, immediately after, 6 and 24 hours, 3 and 7 days, and 1, 3, and 6 months after PCI in 125 patients with stable angina undergoing uncomplicated PCI. Plasminogen levels, OxPL-PLG, and array of 16 oxidative, inflammatory and coagulation biomarkers were measured with established assays. Results OxPL-PLG and plasminogen declined significantly immediately post-PCI, rebounded to baseline, peaked at 3 days and slowly returned to baseline by 6 months (p<0.0001 by ANOVA). The temporal trends to maximal peak in biomarkers were as follows: immediately post PCI: OxPL-apoB and lipoprotein (a); Day 1- the inflammatory biomarkers IL-6 and CRP; Day 3- coagulation biomarkers OxPL-PLG, plasminogen and tissue plasminogen activity; Day 3-7- plasminogen activator inhibitor; and Day 7-30- complement factor H binding to malondialdehyde-LDL, PAI-1 activity, MDA-LDL IgG and IgM, CuOxLDL IgM, and ApoB-IC IgM and IgG. Most of the biomarkers trended to baseline by 6 months. Conclusions PCI results in a specific, temporal sequence of changes in plasma biomarkers. These observations provide insights into the effects of iatrogenic barotrauma and plaque disruption during PCI and suggest avenues of investigation to explain complications of PCI and development of targeted therapies to enhance procedural success.

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

“…There is some plausibility to the theory of immune induction following an oxLDL stimulus: using PCI as an example ( 43 ), studies have shown long-lasting immune system induction to rapid oxLDL increases, with raised IgG and IgM anti-oxLDL antibodies present out to 6 months following the index procedure ( 9 , 44 ). Whilst these studies demonstrated immunomodulation following PCI, we did not find such a trend in this study, with unchanged baseline or post-exercise oxidative biomarkers.…”

Natural products: The role and mechanism in low‐density lipoprotein oxidation and atherosclerosis

“…Is circulating oxLDL transported from solid tissue or oxidized in the blood? For example, in patients undergoing PCI, the peak of oxidized phospholipids immediately increases after surgery, and the effect of immunoglobulin (Ig) on oxLDL decreases (Leibundgut, Lee, Strauss, Segev, & Tsimikas, 2016). However, the presence of oxLDLs has been confirmed in atherosclerotic lesions of humans and rabbits (Yla-Herttuala et al, 1989).…”

In search of a physiological function of lipoprotein(a): causality of elevated Lp(a) levels and reduced incidence of type 2 diabetes

“…However, the closest explanation of Lp(a) biology, but not necessarily the correct one, likely has to do with the fact that the LPA gene has duplicated itself from the plasminogen gene, either to further enhance plasminogen activity or to act as a yin-yang balance to plasminogen pathophysiology. In fact, we have shown that the oxidized phospholipids that are primarily present on Lp(a) are associated with increased cardiovascular risk (21,22), but that the oxidized phospholipids present on plasminogen are associated with enhanced fibrinolysis in vitro and that higher levels are present post-myocardial infarction (23)(24)(25), a putative beneficial function to prevent thrombus propagation. In line with these relationships, several members of the plasminogenrelated coagulation cascade, including tissue plasminogen activator that activates plasminogen to plasmin, are also associated with higher risk of incident T2D (26)(27)(28)(29), another action that is seemingly opposed by elevated Lp(a) levels.…”