DeFilippis Andrew P, Chernyavskiy Ilya, Amraotkar Alok R, Trainor Patrick J, Kothari Shalin, Ismail Imtiaz, Hargis Charles W, Korley Frederick K, Leibundgut Gregor, Tsimikas Sotirios, Rai Shesh N, Bhatnagar Aruni
Division of Cardiovascular Medicine, Department of Medicine, KentuckyOne/Jewish Hospital, University of Louisville, 550 South Jackson Street, Louisville, KY, 40202, USA.
Johns Hopkins University, Baltimore, MD, USA.
J Thromb Thrombolysis. 2016 Jul;42(1):61-76. doi: 10.1007/s11239-015-1292-5.
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.
氧化磷脂(OxPL)在动脉粥样硬化斑块中含量丰富。心肌梗死(MI)后,它们也会与循环中的纤溶酶原结合,并且它们与纤溶酶原的结合可能会增强纤维蛋白溶解作用。我们试图评估急性心肌梗死后循环中纤溶酶原以及与纤溶酶原结合的氧化磷脂(OxPL-PLG)水平是否升高,以及这种升高在动脉粥样硬化血栓形成性(1型)和非动脉粥样硬化血栓形成性(2型)心肌梗死之间是否存在差异。我们在急性心肌梗死后以及稳定型冠状动脉疾病(CAD)血管造影术后的0、6、24、48小时和>3个月(稳定状态)测量了循环中纤溶酶原和OxPL-PLG的水平。49名受试者符合急性心肌梗死标准,其中34例明确为动脉粥样硬化血栓形成性(n = 22)或非动脉粥样硬化血栓形成性(n = 12)心肌梗死;15例患者符合稳定型CAD标准。急性心肌梗死组纤溶酶原和OxPL-PLG的平均基线水平低于稳定型CAD组(纤溶酶原:9.75 vs 20.2,p < 0.0001;OxPL-PLG:165.5 vs 275.1,p = 0.0002),并且在包括3个月随访在内的各个时间点或不同时间点之间均未发生变化。动脉粥样硬化血栓形成性(1型)心肌梗死受试者的纤溶酶原和OxPL-PLG平均基线水平也低于非动脉粥样硬化血栓形成性(2型)心肌梗死受试者(纤溶酶原:8.65 vs 12.1,p < 0.03;OxPL-PLG:164.5 vs 245.7,p = 0.02),并且这种关系在各个时间点或不同时间点之间均未改变。急性心肌梗死患者的纤溶酶原和OxPL-PLG水平低于稳定型CAD患者,也低于动脉粥样硬化血栓形成性心肌梗死(1型)患者与非动脉粥样硬化血栓形成性心肌梗死(2型)患者。这些发现持续至心肌梗死后3个月的中位随访期。纤溶酶原和OxPL-PLG与急性心肌梗死,尤其是动脉粥样硬化血栓形成性心肌梗死(1型)的关联,可能反映了纤维蛋白溶解能力降低,这与动脉粥样硬化血栓形成事件风险增加相关,这种风险增加将稳定型CAD与不稳定型CAD区分开来,以及将动脉粥样硬化血栓形成性心肌梗死(1型)与非动脉粥样硬化血栓形成性心肌梗死(2型)区分开来。有必要进行更大样本量的进一步研究。