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

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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.

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Abbreviations

AAA:

Abdominal aortic aneurysm

ACS:

Acute coronary syndrome

ApoB:

Apolipoprotein B

BP:

Blood pressure

CABG:

Coronary artery bypass graft

CAD:

Coronary artery disease

CEA:

Carotid endarterectomy

CVD:

Cardiovascular disease

EDTA:

Ethylenediamine tetraacetic acid

ELISA:

Enzyme-linked immunosorbent assay

ECG:

Electrocardiogram

LBBB:

Left bundle branch block

MI:

Myocardial infarction

MPG:

Myocardial perfusion grade

OxPL:

Oxidized phospholipids

OxPL-PLG:

Oxidized phospholipids bound to plasminogen

PAI-1:

Plasminogen activator inhibitor-1

PCI:

Percutaneous coronary intervention

PLG:

Plasminogen

STEMI:

ST-segment elevation myocardial infarction

TIA:

Transient ischemic attack

TIMl:

Thrombolysis in myocardial infarction

tPA:

Tissue plasminogen activator

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Acknowledgments

We would like to thank all of the subjects who generously consented to participate in this study. We also appreciate the University of Louisville Diabetes and Obesity Center, the University of Louisville and the KentuckyOne Jewish Hospitals, CVPath Institute, Inc., Gaithersburg, Maryland, and the Johns Hopkins Quantitative Angiographic Core Laboratory. This work was supported in part by a grant from the American Heart Association (11CRP7300003) and the National Institute of General Medical Sciences (GM103492). Dr. Rai was supported by Wendell Cherry Chair in Clinical Trial Research and generous support from Dr. DM Miller, Director James Graham Brown Cancer Center. We thank Dr. Deborah MClellan for editorial assistance.

Disclosures

Sample measurements were made in the laboratory of Dr. Sotirios Tsimikas, University of California, San Diego, La Jolla, California. Coronary aspiration material was evaluated at CVPath Institute, Inc., Gaithersburg, Maryland. Coronary angiography was evaluated at the Johns Hopkins Quantitative Angiographic Core Laboratory, Baltimore, Maryland. Dr. Tsimikas is named as co-inventor and receives royalties from patents owned by the University of California, San Diego, on oxidation-specific antibodies. No author has any relationships with industry pertinent to this work.

Grant support

American Heart Association (11CRP7300003) and National Institute of General Medical Sciences (GM103492).

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Authors and Affiliations

  1. Division of Cardiovascular Medicine, Department of Medicine, KentuckyOne/Jewish Hospital, University of Louisville, 550 South Jackson Street, Louisville, KY, 40202, USA

    Andrew P. DeFilippis, Alok R. Amraotkar & Aruni Bhatnagar

  2. Johns Hopkins University, Baltimore, MD, USA

    Andrew P. DeFilippis

  3. Department of Physiology, University of Louisville, Louisville, KY, USA

    Ilya Chernyavskiy

  4. Division of Cardiovascular Medicine, and Bioinformatics, Department of Medicine, University of Louisville, Louisville, KY, USA

    Patrick J. Trainor

  5. Department of Medicine, SUNY Upstate Medical University, Syracuse, NY, USA

    Shalin Kothari

  6. Department of Medicine, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA

    Imtiaz Ismail

  7. School of Medicine, University of Louisville, Louisville, KY, USA

    Charles W. Hargis

  8. Department of Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Frederick K. Korley

  9. Division of Cardiology, University of Basel, Basel, Switzerland

    Gregor Leibundgut

  10. Division of Cardiovascular Medicine, Department of Medicine, University of California San Diego, La Jolla, CA, USA

    Sotirios Tsimikas

  11. Department of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY, USA

    Shesh N. Rai

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  1. Andrew P. DeFilippis
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Correspondence to Andrew P. DeFilippis.

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DeFilippis, A.P., Chernyavskiy, I., Amraotkar, A.R. et al. Circulating levels of plasminogen and oxidized phospholipids bound to plasminogen distinguish between atherothrombotic and non-atherothrombotic myocardial infarction. J Thromb Thrombolysis 42, 61–76 (2016). https://doi.org/10.1007/s11239-015-1292-5

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