Circulating levels of plasminogen and oxidized phospholipids bound to plasminogen distinguish between atherothrombotic and non-atherothrombotic myocardial infarction

Abstract

Oxidized phospholipids (OxPL) are abundant in atherosclerotic plaques. They are also bound to circulating plasminogen after myocardial infarction (MI), and their binding to plasminogen may accentuate fibrinolysis. We sought to assess whether circulating levels of plasminogen and OxPL bound to plasminogen (OxPL-PLG) increase following acute MI and whether this increase differs between atherothrombotic (Type 1) and non-atherothrombotic (Type 2) MI. We measured circulating levels of plasminogen and OxPL-PLG at 0, 6, 24, 48 h, and >3 months (stable state) following acute MI and following an angiogram for stable coronary artery disease (CAD). Forty-nine subjects met the criteria for acute MI, of whom 34 had clearly defined atherothrombotic (n = 22) or non-atherothrombotic (n = 12) MI; 15 patients met the criteria for stable CAD. Mean baseline levels of plasminogen and OxPL-PLG were lower in the acute MI group than in the stable CAD group (9.75 vs 20.2, p < 0.0001 for plasminogen and 165.5 vs 275.1, p = 0.0002 for OxPL-PLG) and did not change over time or between time points, including the 3-month follow-up. Mean baseline levels of plasminogen and OxPL-PLG were also lower in atherothrombotic (Type 1) than in non-atherothrombotic (Type 2) MI subjects (8.65 vs 12.1, p < 0.03 for plasminogen and 164.5 vs 245.7, p = 0.02 for OxPL-PLG), and this relationship did not change over time or between time points. Plasminogen and OxPL-PLG were lower in patients presenting with an acute MI than in those with stable CAD and also in those with atherothrombotic MI (Type 1) vs. those with non-atherothrombotic MI (Type 2). These findings persisted at a median follow-up of 3 months post-MI. The association of plasminogen and OxPL-PLG with acute MI, particularly atherothrombotic MI (Type 1), could reflect a reduced fibrinolytic capacity, associated with an increased risk of atherothrombotic events differentiating stable CAD from unstable CAD and atherothrombotic MI (Type 1) from non-atherothrombotic MI (Type 2). Additional study with a larger sample size is warranted.

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

“…For example, in a recent study,(39) we showed mean baseline levels of plasminogen and OxPL-PLG were lower in acute MI than in the stable CAD, consistent with prior data. (11) However, mean baseline levels of plasminogen and OxPLPLG were also lower in atherothrombotic versus non-atherothrombotic MI.…”

Systems characterization of differential plasma metabolome perturbations following thrombotic and non-thrombotic myocardial infarction

“…A patient cohort was recruited to allow for determining the unique plasma metabolomic signature of AMI differentiated by proximate cause 14 . A novel criteria was developed for discriminating between thrombotic and non-thrombotic MI patients as widely accepted guidelines for such discrimination were unavailable.…”

Inferring metabolite interactomes via molecular structure informed Bayesian graphical model selection with an application to coronary artery disease

“…In order to determine changes in the plasma metabolome associated with myocardial infarction (MI) characterized by thrombotic etiology versus non-thrombotic etiology, DeFilippis and colleagues assembled a human cohort as previously described (DeFilippis et al, 2016;DeFilippis et al, 2017;Trainor et al, 2017). Briefly, 80 human subjects presenting with suspected acute MI or stable coronary artery disease (CAD) were enrolled.…”