Elevated Levels of Shed Membrane Microparticles With Procoagulant Potential in the Peripheral Circulating Blood of Patients With Acute Coronary Syndromes

Abstract

Background-Apoptotic microparticles are responsible for almost all tissue factor activity of the plaque lipid core. We hypothesized that elevated levels of procoagulant microparticles could also circulate in the peripheral blood of patients with recent clinical signs of plaque disruption and thrombosis. Methods and Results-We studied 39 patients with coronary heart disease, including 12 patients with stable angina and 27 patients with acute coronary syndromes (ACS), and 12 patients with noncoronary heart disease. We isolated the circulating microparticles by capture with annexin V and determined their procoagulant potential with a prothrombinase assay. The cell origins of microparticles were determined in an additional 22 patients by antigenic capture with specific antibodies. A cute coronary syndromes (ACS) are severe clinical manifestations of coronary artery lumen occlusion by a thrombus formed on the contact of a ruptured or eroded atherosclerotic plaque. 1,2 Tissue factor (TF) is highly expressed in atherosclerotic plaques, 3 and TF activity of plaques retrieved from patients with unstable angina (UA) is significantly higher than that found in the plaques of patients with stable angina (SA), 4 which suggests that it may significantly determine thrombus formation after plaque disruption. TF activity is highly dependent on the presence of phosphatidylserine (PS), 5 and it has been shown that this anionic phospholipid is redistributed on the cell surface during apoptotic death, 6 conferring to the cell a potent procoagulant activity. 7,8 Interestingly, shed membrane apoptotic microparticles rich in PS are produced in considerable amounts within human atherosclerotic plaques and carry almost all TF activity of the plaque lipid core, 9 indicating that they may largely determine plaque thrombogenicity. In the present study, we hypothesized that high levels of cell-derived microparticles with procoagulant potential could also be detectable in the circulating blood of patients with recent clinical signs of plaque disruption and thrombosis and may therefore contribute to the initiation and perpetuation of the thrombotic process. Methods Patient SelectionTo isolate the circulating microparticles and determine their procoagulant potential, we prospectively included 39 patients with angina and angiographic documentation of coronary artery disease (CAD) and 12 controls. Among patients with CAD, 12 (9 men; mean age 62Ϯ3 years) had SA with no signs of myocardial ischemia at rest, and 27 had ACS: 13 (8 men; mean age 62Ϯ4 years) had UA (Braunwald class III) with documented signs of recent myocardial ischemia at rest, and 14 (10 men; mean age 61Ϯ4 years) had acute myocardial infarction (MI). Cardiovascular risk factors were not significantly different between the 3 groups of patients with CAD, except for hypercholesterolemia, which was more prevalent in patients with SA (PϽ0.02).All coronary patients were receiving aspirin. Patients with ACS received additional standard antithrombotic therapy before blood sampling. Anti-isch...

Vβ‐restricted T cell adherence to endothelial cells: A mechanism for superantigen‐dependent vascular injury

“…It is known, however, that microparticles rich in phosphatidylserine can participate in the dissemination of proadhesive and procoagulant activities in thrombotic disorders (11,16,17,26,34), a property which could potentially contribute to the vascular pathology seen in vasculitic syndromes.…”

“…Moreover, plasma from patients with APS, MS, or TTP was shown to induce the formation of EMPs from endothelial cells in tissue culture (11,18,19). EMPs exhibit prothrombotic potential, which is mediated by activation of the extrinsic coagulation pathway (i.e., the tissue factor/factor VII-dependent pathway) (11,16,17,(21)(22)(23).…”

Endothelial dysfunction in cardiovascular disease and Flammer syndrome—similarities and differences

“…Besides different advantages in technical ease, invasiveness, and reliability, a major difference is whether macro-or microvascular beds are intended to be examined. Biomarkers such as ET-1, circulating endothelial microparticles, and progenitor cells can be analyzed [28].…”

Signaling pathways involved in OxPAPC-induced pulmonary endothelial barrier protection

“…Enhanced lipid peroxidation leading to formation of oxidized phospholipids was observed in acute lung injury syndromes such as ARDS, ventilator-induced lung injury, and asthma (Chabot, Mitchell et al 1998;Wood, Gibson et al 2003). An increased release of membrane vesicles containing oxidized phospholipids has been detected as a result of tissue injury and apoptosis (Holme, Solum et al 1994;Huber, Vales et al 2002), and such membrane vesicles were also observed in patients with acute lung injury, cardiac ischemia, acute coronary syndrome and in pathological settings with platelet activation (Holme, Solum et al 1994;Mallat, Benamer et al 2000).…”