thromboplastin and Acute-Coronary-Syndrome

The term microparticle (MP) identifies a heterogeneous population of vesicles playing a relevant role in the pathogenesis of vascular diseases, cancer and metabolic diseases such as diabetes mellitus. MPs are released by virtually all cell types by shedding during cell growth, proliferation, activation, apoptosis or senescence processes. MPs, in particular platelet- and endothelial-derived MPs (PMPs and EMPs), are increased in a wide range of thrombotic disorders, with an interesting relationship between their levels and disease pathophysiology, activity or progression. EMP plasma levels have been associated with several cardiovascular diseases and risk factors. PMPs are also shown to be involved in the progressive formation of atherosclerotic plaque and development of arterial thrombosis, especially in diabetic patients. Indeed, diabetes is characterised by an increased procoagulant state and by a hyperreactive platelet phenotype, with enhanced adhesion, aggregation, and activation. Elevated MP levels, such as TF+ MPs, have been shown to be one of the procoagulant determinants in patients with type 2 diabetes mellitus. Atherosclerotic plaque constitutes an opulent source of sequestered MPs, called "plaque" MPs. Otherwise, circulating MPs represent a TF reservoir, named "blood-borne" TF, challenging the dogma that TF is a constitutive protein expressed in minute amounts. "Blood-borne" TF is mainly harboured by PMPs, and it can be trapped within the developing thrombus. MP detection and enumeration by polychromatic flow cytometry (PFC) have opened interesting perspectives in clinical settings, particularly for the evaluation of MP numbers and phenotypes as independent marker of cardiovascular risk, disease and outcome in diabetic patients.

Topics: Acute Coronary Syndrome; Atherosclerosis; Biomarkers; Blood Platelets; Cardiovascular Diseases; Cell-Derived Microparticles; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Endothelial Cells; Humans; Plaque, Atherosclerotic; Risk Factors; Stroke; Thromboplastin

It is generally accepted that the initial event in coagulation and intravascular thrombus formation is the exposure of the flowing blood to cell-surface protein, such as tissue factor (TF). Vascular injury and/or atherosclerotic plaque complication is responsible for this exposure, leading to clinical manifestations such as acute coronary syndromes. For many years, TF has been considered one of the major determinants of plaque-related thrombosis. However, the discoveries of different pools of TF that circulates in the blood as cell-associated TF, microparticles bound, and as soluble form have changed this dogma. Recent evidence suggests that an increased circulating TF activity may potentiate the initial thrombogenic stimulus related to vessel wall-associated TF, leading to the formation of larger and/or more stable thrombus and thus more severe clinical manifestations. Different pathological conditions, such as inflammatory status, enhance TF expression and activity. Conversely, TF upregulation may facilitate inflammation by formation of proinflammatory fibrin fragments and coagulation proteases generation, including FVIIa, FXa, and thrombin. Furthermore, the biology of TF has become more complex by the demonstration that, apart from its known effects on blood coagulation, it is involved in intracellular signaling, proliferation, angiogenesis, and tumor metastasis.

Topics: Acute Coronary Syndrome; Animals; Blood Coagulation; Blood Platelets; Cell Proliferation; Cell-Derived Microparticles; Factor VIIa; Factor Xa; Humans; Plaque, Atherosclerotic; Signal Transduction; Thromboplastin; Thrombosis

Tissue factor (TF) is a 47-kDa transmembrane glycoprotein and the main initiator of the blood coagulation cascade. Binding to its ligand factor VIIa (FVIIa) also initiates noncoagulant signaling with broad biological implications. In this review, we discuss how TF interacts with other cell-surface proteins, which affect biological functions such as cell migration and cell survival. A vast number of publications have demonstrated the importance of TF-induced activation of protease-activated receptors, but recently published research has indicated a more complicated picture. As it has been discovered that TF interacts with integrins and receptor tyrosine kinases, novel signaling mechanisms for the TF/FVIIa complex have been presented. The knowledge of these new aspects of TF signaling may, for instance, facilitate the development of new treatment strategies for cancer and acute coronary syndromes, two examples of diseases characterized by aberrant TF expression and signaling.

Topics: Acute Coronary Syndrome; Animals; Apoptosis; Cell Movement; Cell Survival; Factor VIIa; Gene Expression Regulation, Neoplastic; Humans; Neoplasm Proteins; Neoplasms; Protein Binding; Signal Transduction; Thromboplastin

From acute coronary syndrome (ACS) to the prevention of cardioembolic events in patients with atrial fibrillation and thrombosis of mechanical heart valves, there is a quest to develop a new generation of anticoagulants. Perhaps the 'holy grail' of antithrombotic therapy is not only a drug that will prevent coagulation without promoting bleeding but also an anticoagulant that is easily reversible should the clinical need arise. Further, an optimally designed anticoagulant would have broad applications to include arterial, venous, hybrid conditions (atrial flutter and fibrillation) and nonbiological materials. Factor (F)IXa plays a pivotal part in tissue factor (TF)-mediated thrombin generation, and therefore represents a potentially promising target for drug development. FIXa activity has been targeted by multiple modalities, including oral inhibitors, RNA aptamers, monoclonal antibodies and synthetic active-site-blocking competitive inhibitors. Herein, we summarize the biochemistry of FIXa as it applies to thrombotic disorders and conditions, as well as the evolution of targeted therapies.

Topics: Acute Coronary Syndrome; Animals; Anticoagulants; Atrial Fibrillation; Drug Design; Factor IXa; Hemorrhage; Humans; Thrombin; Thromboplastin; Thrombosis

The term "vulnerable plaque" identifies atherosclerotic lesions prone to rupture. Plaque disruption facilitates the interaction of the inner components of the lesion, tissue factor (TF) among them, with the flowing blood. This results in activation of the coagulation cascade, ultimately leading to thrombus formation, and abrupt vascular occlusion. Despite the central role of vulnerable plaques in the onset of acute coronary syndromes (ACS), there are certain conditions (e.g., eroded plaques) where a hyperactive, "vulnerable" blood, may play a predominant pathophysiological role. Recently, two distinct pools of circulating TF have been identified. One, associated with cell-derived microparticles probably originating from apoptotic cells, such as macrophages, smooth muscle cells, and endothelium. The most recent, blood-borne TF, circulates in an "inactive" form (encryption) and has to be activated (decryption) to exert its thrombogenic activity. Certain pathological conditions associated with an increased rate of thrombotic complications have been associated with high levels of circulating TF. It is thought that the blood-borne TF perpetuates the initial thrombogenic stimulus, leading to the formation of larger or more stable thrombus, and thus, more severe ACS. Thus, the concept of vulnerable blood could represent a new link between the vulnerable lesion and the high-risk patient. Therefore, the assessment of selected biomarkers associated with "vulnerable or hyperreactive blood", e.g., blood-borne tissue factor, may represent a useful tool to identify patients with a high-risk profile of developing major cardiovascular events.

Topics: Acute Coronary Syndrome; Atherosclerosis; Biomarkers; Cell-Derived Microparticles; Coronary Artery Disease; Humans; Thromboplastin

Atherothrombosis--defined as atherosclerotic lesion disruption with superimposed thrombus formation--is a leading cause of death in patients with diabetes mellitus. Platelets play a pivotal role in atherothrombosis and platelets of diabetic patients are hyperreactive. Numerous studies have investigated the usefulness of antiplatelet therapy for primary and secondary prevention of atherothrombotic events in diabetic patients. However, there are limited evidences that aspirin may be effective in the reduction of atherothrombotic complication in this population. Additionally, dual antiplatelet therapy with aspirin and clopidogrel has been suggested to be harmful. In contrast, the role of antiplatelet therapy in secondary prevention after ischemic cardiac events is well established in diabetes. Glycoprotein IIb/IIIa receptor antagonists can reduce mortality in diabetic patients committed to undergo percutaneous coronary intervention (PCI). Upregulation of P2Y(12) signalling occurs in hyperglycemia, and the relevance of platelet P2Y(12) receptor inhibition with prasugrel in reducing adverse events following PCI has been recently suggested. Besides platelet activation, several other mechanisms may be involved in the pathophysiology of diabetic atherothrombosis. Tissue factor (TF)-bearing procoagulant microparticles (MPs) are a heterogeneous population of membrane-coated vesicles released by several cell lines upon activation or apoptosis. There is converging evidence that MPs and MP-associated TF activity are upregulated in patients with diabetes mellitus and can participate actively in promoting atherothrombotic complications. In this context, drugs that may reduce the release of microparticles and/or their thrombogenic capacity has the potential to improve upon current antiplatelet therapy, possibly resulting in lower adverse events rates in diabetic individuals.

Topics: Acute Coronary Syndrome; Apoptosis; Aspirin; Blood Platelets; Clopidogrel; Diabetes Complications; Diabetes Mellitus; Glycoproteins; Humans; Models, Biological; Piperazines; Platelet Activation; Prasugrel Hydrochloride; Receptors, Purinergic P2Y12; Thiophenes; Thromboplastin; Thrombosis; Ticlopidine

In the guidelines for patients with acute coronary syndrome (ACS), reperfusion, antiplatelet treatment, completed with parenteral anticoagulant are the standard therapy. It is because ACS is the result of occlusion of related artery by thrombus compound mostly of platelets, with processes of aggregation and adhesion in its pathogenesis. However, many patients after ACS experience major adverse cardiovascular events (MACE) despite optimal long term antiplatelet therapy. The possible reasons seem to be not only the resistance to this drugs but also underestimated coagulation processes. This review describes the dysfunction of particular coagulation parameters in patients with coronary artery disease and their relationship with MACE after ACS.

Topics: Acute Coronary Syndrome; Anticoagulants; Antithrombins; Blood Coagulation Disorders; Fibrinogen; Fibrinopeptide A; Humans; Peptide Fragments; Platelet Aggregation Inhibitors; Protein Precursors; Prothrombin; Thromboplastin; von Willebrand Factor

The aim of this overview is to summarize the available data on the involvement of monocytes in the pathological processes related to the development of acute coronary syndromes and the recovery of damaged areas, the prevention of excessive inflammatory and procoagulant response, and the restoration of microcirculation (angiogenesis).

Topics: Acute Coronary Syndrome; Animals; Blood Platelets; Cell Communication; Chemokine CCL2; Coronary Artery Disease; Endothelial Cells; Humans; Inflammation; Lipoproteins, LDL; Monocytes; Stem Cells; Thromboplastin

It remains uncertain why some plaque ruptures trigger acute coronary syndrome (ACS), whereas others do not. We investigated the anatomic features and tissue factor (TF) expression at the sites of plaque rupture in 42 patients presenting with ACS (n = 23) or stable angina (n = 19). Intravascular ultrasound examination was performed before directional coronary atherectomy. Specimens were stained with antibodies against TF, CD68 positive phagocytic cells, and smooth muscle cells; and intravascular ultrasound and immunohistochemistry results were compared. Baseline demographic and clinical characteristics, as well as vessel and lumen sizes at both reference and lesion sites, were comparable in the two groups. However, the remodeling index and plaque burden at lesion sites were significantly greater in the ACS than in the stable angina group. The TF-immunopositive areas were significantly greater in the ACS than in the stable angina group (0.07%; IQR [0.02-0.16%] vs. 0.02%; IQR [0.01-0.05%], P = 0.022), whereas the proportions of CD68-positive and smooth muscle cell areas were similar. There was a significant correlation between areas positive for TF and those positive for CD68 (r = 0.83, P < 0.001). In conclusion, ruptured plaques in patients with ACS show stronger TF expression, a greater plaque burden, and a higher remodeling index than do plaques in those with stable angina, suggesting that both lesion morphology and local thrombogenicity are related to clinical symptoms after plaque rupture.

Topics: Acute Coronary Syndrome; Adult; Aged; Angina Pectoris; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Female; Gene Expression Regulation; Humans; Male; Middle Aged; Myocytes, Smooth Muscle; Phagocytes; Plaque, Atherosclerotic; Rupture, Spontaneous; Thromboplastin

Our study sought to evaluate mechanisms of the current strategies for optimal anticoagulation during percutaneous coronary intervention (PCI).. Thirty-two high risk acute coronary syndrome patients were randomised to bivalirudin and provisional GPIIb/IIIa inhibition (GPIIb/IIIa) or unfractionated heparin (UFH) and mandatory GPIIb/IIIa. Flow cytometric measurements immediately after anticoagulation showed that, unlike UFH, bivalirudin did not activate platelets as indicated by P-selectin expression and fibrinogen binding while decreasing platelet-monocyte aggregates and monocyte expression of tissue factor. UFH released tissue factor pathway inhibitor (TFPI) during and immediately after PCI while bivalirudin (irrespective of GP IIb/IIIa) did not. Lower levels of TFPI with bivalirudin were seen during and immediately after PCI (P<0.01). Thrombin generation as indicated by prothrombin fragment F 1+2 levels was reduced during PCI in the UFH group (P<0.01) but not with bivalirudin. Soluble CD40 ligand is associated with thrombosis and levels were higher in the bivalirudin group irrespective of GPIIb/IIIa at the same stages (P<0.05).. Bivalirudin has some early advantages on platelet activation when compared to UFH. However, there are significant limitations in its mechanism of action, particularly a lack of release of tissue factor pathway inhibitor.

Topics: Acute Coronary Syndrome; Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Biomarkers; Blood Coagulation; CD40 Ligand; Clopidogrel; Drug Therapy, Combination; Female; Fibrinogen; Heparin; Hirudins; Humans; Lipoproteins; Male; Membrane Glycoproteins; Middle Aged; Monocytes; Peptide Fragments; Platelet Activation; Platelet Adhesiveness; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prothrombin; Recombinant Proteins; Thromboplastin; Thrombosis; Ticlopidine; Treatment Outcome

Several studies have shown that T-cells might be involved in pathophysiology of acute coronary syndromes (ACS). Tissue factor (TF) plays a key role in ACS. Many evidences have indicated that some statins reduce TF expression in several cell types. However, literature about rosuvastatin and TF and about statins effects on T-cells is still scanty. Colchicine is an anti-inflammatory drug recently proven to have beneficial effects in ACS via unknown mechanisms. This study investigates the effects of colchicine and rosuvastatin on TF expression in oxLDL-activated T-cells. T-cells, isolated from buffy coats of healthy volunteers, were stimulated with oxLDL (50 µg/dL). T-cells were pre-incubated with colchicine (10 µM) or rosuvastatin (5 µM) for 1 h and then stimulated with oxLDL (50 μg/mL). TF gene (RT-PCR), protein (western blot), surface expression (FACS) and procoagulant activity (FXa generation assay) were measured. NF-κB/IκB axis was examined by western blot analysis and translocation assay. Colchicine and rosuvastatin significantly reduced TF gene, and protein expression and procoagulant activity in oxLDL stimulated T-cells. This effect was associated with a significant reduction in TF surface expression as well as its procoagulant activity. These phenomena appear modulated by drug effects on the transcription factor NF-kB. Rosuvastatin and colchicine prevent TF expression in oxLDL-stimulated T-cells by modulating the NF-κB/IκB axis. Thus, we speculate that this might be another mechanism by which these drugs exert benefic cardiovascular effects.

Topics: Acute Coronary Syndrome; Colchicine; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipoproteins, LDL; NF-kappa B; Rosuvastatin Calcium; T-Lymphocytes; Thromboplastin

Topics: Acute Coronary Syndrome; Biomarkers; Coronary Angiography; Coronary Circulation; Female; Humans; Male; Pregnancy; Pregnancy-Associated Plasma Protein-A; Thromboplastin

Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase with a controversial role in pathophysiology of cardiovascular disease. It seems involved in progression of atherosclerosis and is widely represented in atherosclerotic plaque. PAPP-A plasma levels are elevated in patients with acute coronary syndromes (ACS), thus it has been suggested that it might be a prognostic marker for developing major cardiovascular events. However, the pathophysiological link(s) between PAPP-A and ACS are still unknown. Several studies have indicated that tissue factor (TF) plays a pivotal role in the pathophysiology of ACS by triggering the formation of intracoronary thrombi following endothelial injury. This study investigates whether PAPP-A, at concentrations measurable in ACS patients, might induce TF expression in human endothelial cells in culture (HUVEC). In HUVEC, PAPP-A induced TF-mRNA transcription as demonstrated by real time PCR and expression of functionally active TF as demonstrated by FACS analysis and pro-coagulant activity assay. PAPP-A induced TF expression through the activation of Akt/NF-κB axis, as demonstrated by luciferase assay and by suppression of TF-mRNA transcription as well as of TF expression/activity by Akt and NF-κB inhibitors. These data indicate that PAPP-A promotes TF expression in human endothelial cells and support the hypothesis that this proteinase, besides being involved in progression of atherosclerosis, does not represent an independent risk factor for adverse cardiovascular events, but it rather might play an "active" role in the pathophysiology of ACS as an effector molecule able to induce a pro-thrombotic phenotype in endothelial cells.

Topics: Acute Coronary Syndrome; Blood Coagulation; Endothelial Cells; Female; Human Umbilical Vein Endothelial Cells; Humans; NF-kappa B; Pregnancy; Pregnancy-Associated Plasma Protein-A; Proto-Oncogene Proteins c-akt; Thromboplastin

Current methods for distinguishing acute coronary syndromes such as heart attack from stable coronary artery disease, based on the kinetics of thrombin formation, have been limited to evaluating sensitivity of well-established chemical species (e.g., thrombin) using simple quantifiers of their concentration profiles (e.g., maximum level of thrombin concentration, area under the thrombin concentration versus time curve). In order to get an improved classifier, we use a 34-protein factor clotting cascade model and convert the simulation data into a high-dimensional representation (about 19000 features) using a piecewise cubic polynomial fit. Then, we systematically find plausible assays to effectively gauge changes in acute coronary syndrome/coronary artery disease populations by introducing a statistical learning technique called Random Forests. We find that differences associated with acute coronary syndromes emerge in combinations of a handful of features. For instance, concentrations of 3 chemical species, namely, active alpha-thrombin, tissue factor-factor VIIa-factor Xa ternary complex, and intrinsic tenase complex with factor X, at specific time windows, could be used to classify acute coronary syndromes to an accuracy of about 87.2%. Such a combination could be used to efficiently assay the coagulation system.

Topics: Acute Coronary Syndrome; Algorithms; Blood Coagulation; Blood Coagulation Factors; Coronary Artery Disease; Decision Trees; Humans; Kinetics; Models, Biological; Molecular Dynamics Simulation; Thrombin; Thromboplastin; Time Factors

T-lymphocyte activation plays an important role in the pathophysiology of acute coronary syndromes (ACS). Plaques from ACS patients show a selective oligoclonal expansion of T-cells, indicating a specific, antigen-driven recruitment of T-lymphocytes within the unstable lesions. At present, however, it is not known whether T-cells may contribute directly to thrombosis by expressing functional tissue factor (TF). Accordingly, the aim of the present study was to investigate whether T-cells are able to express functional TF in their activated status.. In vitro, CD3(+)-cells, isolated from buffy coats, were stimulated with anti-CD3/CD28 beads, IL-6, TNF-α, IL-17, INF-γ or PMA/ionomycin. Following stimulation, TF expression on cell-surface, at gene and protein levels, as well as its procoagulant activity in whole cells and microparticles was measured. In vivo, TF expression was evaluated in CD3(+)-cells isolated from the aorta and the coronary sinus of ACS-NSTEMI and stable coronary artery disease (SCAD) patients. The presence of CD3(+)-TF(+)cells was also evaluated by immunohistochemistry in thrombi aspirated from ACS-STEMI patients.. PMA/ionomycin and IL-17 plus INF-γ stimulation resulted in a significant TF increase at gene and protein levels as well as at cell-surface expression. This was accompanied by a parallel increase in FXa generation, both in whole cells and in microparticles, indicating that the induced membrane-bound TF was active. Furthermore, transcardiac TF gradient was significantly higher in CD3(+)-cells obtained from ACS-patients compared to SCAD-patients. Interestingly, thrombi from ACS-STEMI patients resulted enriched in CD3(+)-cells, most of them expressing TF.. Our data demonstrate that activated T-lymphocytes in vitro express functional TF on their membranes, suggesting a direct pathophysiological role of these cells in the thrombotic process; this hypothesis is further supported by the observations in vivo that CD3(+)-cells from coronary circulation of ACS-NSTEMI patients show increased TF levels and that coronary thrombi from ACS-STEMI patients are enriched in CD3(+)-cells expressing TF.

Topics: Acute Coronary Syndrome; Aged; Cells, Cultured; Coronary Angiography; Female; Humans; In Vitro Techniques; Lymphocyte Activation; Male; Middle Aged; Signal Transduction; T-Lymphocytes; Thromboplastin; Thrombosis

Studies suggested that the activation of the coagulation system and inflammation mutually may reinforce each other in some cases. In this study, we test the plasma tissue factor (TF) and interleukin 18 in patients with coronary heart disease (CHD) before and after treatment and aim to determine whether this relationship exists in patients with CHD. The levels of plasma TF and IL-18 from 118 patients with CHD were determined by enzyme-linked immunosorbent assay. One hundred and eighteen patients were divided into acute coronary syndrome (ACS) group (61 cases) and stable angina pectoris group (51 cases). Upon admission, patients with ACS showed significantly higher levels of plasma TF and interleukin 18 compared with those having stable angina (P < 0.01), and the levels decreased after treatment; levels of plasma TF and interleukin 18 of patients with ACS were closely and positively correlated (r = 0.74, P < 0.01); after 7 days of treatment, the correlation decreased (r = 0.53, P > 0.05); and after 1 month of treatment, no significant correlation can be detected between the two (r = 0.18, P > 0.05). The results suggest that levels of plasma TF and interleukin 18 are significantly increased in patients with ACS, and there is significant correlation between the two, indicating an interaction between inflammation and coagulation in patients with ACS and an important role of these two in the occurrence and development of such disease.

Topics: Acute Coronary Syndrome; Aged; Biomarkers; Female; Follow-Up Studies; Humans; Interleukin-18; Male; Middle Aged; Percutaneous Coronary Intervention; Thromboplastin

Circulating ('blood-borne') tissue factor (TF) is implicated in the pathogenesis of several chronic conditions, most notably cardiovascular disease, diabetes, and cancer. Full-length TF is an integral membrane protein, while alternatively spliced TF (asTF) can be secreted and, owing to its unique C-terminus, selectively detected in bio-specimens. The predictive and/or prognostic value of asTF in the circulation is unknown. In a retrospective study, we measured levels of circulating asTF in healthy subjects and individuals with acute coronary syndrome (ACS), diabetes mellitus (DM), ongoing ACS + DM, and pancreatic ductal adenocarcinoma (PDAC).. The prototype-tailored procedure (Diagnostica Stago) was used to measure asTF in plasma from 205 subjects.. There was no significant difference between the proportion of healthy subjects with asTF ≥200 pg/mL and those with ACS, DM, or ACS + DM. The proportion of pancreatic cancer patients (n = 43; PDAC: 42; pancreatic neuroendocrine tumor: 1) with asTF levels ≥200 pg/mL was significantly higher than in healthy subjects; asTF levels ≥200 pg/mL were detected more often in patients with unresectable disease irrespective of initial evaluation and/or preoperative carbohydrate antigen 19-9 (CA19-9) levels.. While asTF levels ≥200 pg/mL are not observed with increased frequency in patients with ACS and/or DM, they do occur more frequently in the plasma of patients with pancreatic cancer and are associated with lower likelihood of tumor resectability, irrespective of the preoperative diagnosis. asTF may thus have utility as a novel marker of aggressive pancreatic tumor phenotype.

Topics: Acute Coronary Syndrome; Alternative Splicing; Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Case-Control Studies; Diabetes Mellitus; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Pancreatic Neoplasms; Prognosis; Retrospective Studies; Thromboplastin

Acute coronary syndrome (ACS) is a major cause of mortality worldwide. We have previously shown that increased interleukin-10 (IL-10) levels are associated with poor outcome in ACS patients.. We performed a genome-wide association study in 2864 ACS patients and 408 healthy controls, to identify genetic variants associated with IL-10 levels. Then haplotype analyses of the identified loci were done and comparisons to levels of IL-10 and other known ACS related biomarkers.. Genetic variants at the ABO blood group locus associated with IL-10 levels (top SNP: rs676457, P = 4.4 × 10-10) were identified in the ACS patients. Haplotype analysis, using SNPs tagging the four main ABO antigens (A1, A2, B and O), showed that O and A2 homozygous individuals, or O/A2 heterozygotes have much higher levels of IL-10 compared to individuals with other antigen combinations. In the ACS patients, associations between ABO antigens and von Willebrand factor (VWF, P = 9.2 × 10-13), and soluble tissue factor (sTF, P = 8.6 × 10-4) were also found. In the healthy control cohort, the associations with VWF and sTF were similar to those in ACS patients (P = 1.2 × 10-15 and P = 1.0 × 10-5 respectively), but the healthy cohort showed no association with IL-10 levels (P>0.05). In the ACS patients, the O antigen was also associated with an increased risk of cardiovascular death, all causes of death, and recurrent myocardial infarction (odds ratio [OR] = 1.24-1.29, P = 0.029-0.00067).. Our results suggest that the ABO antigens play important roles, not only for the immunological response in ACS patients, but also for the outcome of the disease.

Topics: ABO Blood-Group System; Acute Coronary Syndrome; Adult; Aged; Female; Genome-Wide Association Study; Haplotypes; Humans; Interleukin-10; Male; Middle Aged; Polymorphism, Single Nucleotide; Risk Factors; Thromboplastin; von Willebrand Factor

Thrombus formation is determined by the balance between pro- thrombotic mediators and anti-thrombotic factors.High-density lipoprotein (HDL) from healthy subjects exerts anti-thrombotic properties. Whether this is also the case for HDL from patients with stable coronary heart disease (CHD) or acute coronary syndrome (ACS) is unknown.In human aortic endothelial cells in culture,HDL (50 µg/ml) from healthy subjects (HS) inhibited thrombin-induced tissue factor (TF) expression and activity, while HDL (50 µg/ml) from CHD and ACS patients did not. Similarly, only healthy HDL increased endothelial tissue factor pathway inhibitor (TFPI) expression and tissue plasminogen activator (tPA) release, while HDL from CHD and ACS patients had no effect. Healthy HDL inhibited thrombin-induced plasminogen activator inhibitor type 1 (PAI-1) expression, while HDL from ACS patients enhanced endothelial PAI-1 expression. Inhibition of nitric oxide (NO) formation with L-NAME (100 µmol/l) abolished the anti-thrombotic effects of healthy HDL on TF, TFPI, and tPA expression. The exogenous nitric oxide donor, DETANO, mimicked the effects of healthy HDL and counterbalanced the loss of anti-thrombotic effects of HDL from CHD and ACS patients in endothelial cells. In line with this observation, healthy HDL, in contrast to HDL from CHD and ACS patients, increased endothelial NO production. In the laser-injured carotid artery of the mouse, thrombus formation was delayed in animals treated with healthy HDL compared with mice treated with vehicle or HDL from patients with CHD or ACS. In conclusion, HDL from CHD and ACS patients loses the ability of healthy HDL to suppress TF and to increase TFPI and t-PA and instead enhances PAI-1 and arterial thrombus formation.

Topics: Acute Coronary Syndrome; Adult; Aged; Animals; Aorta; Blood Coagulation; Carotid Artery Injuries; Cells, Cultured; Coronary Disease; Disease Models, Animal; Endothelial Cells; Humans; Lipoproteins; Lipoproteins, HDL; Mice; Middle Aged; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitroso Compounds; Plasminogen Activator Inhibitor 1; Platelet Aggregation; Thrombin; Thromboplastin; Tissue Plasminogen Activator

This study was performed to gain further insight in pro- and anticoagulant characteristics of leukocytes in acute coronary syndrome (ACS). For this purpose, patients presenting on the emergency department (ED) with anginal chest pain were included in this study. In peripheral blood, procoagulant tissue factor (TF) expression was measured in the different blood-borne phagocytes, i.e. neutrophilic granulocytes and the three different monocyte subsets based on expression of CD14 and CD16. Simultaneously, intracellular presence of platelet-(CD41) and/or endothelial cell-remnants (CD62e) was analysed in these different leukocyte subsets. Neutrophils showed a weak intracellular staining of CD62e and CD41 that increased with severity of ACS. Monocytes, and especially the classical (CD14++CD16-) and intermediate monocytes (CD14++CD16+) showed a clear and significant increase in intracellular CD41-staining after coronary damage. The different monocyte subsets showed an increase in expression of TF in severe ACS. Finally, it appeared that also neutrophils showed a significant increase in expression of TF on their membrane. In conclusion, this study showed an increased intracellular staining in blood-borne phagocytes for CD62e and CD41 in patients with ACS compared to non-cardiac related control patients. This indicates that at least in the acute phase of ACS phagocytosis of platelet and endothelial cell-remnants is increased. These data support the recent hypothesis that neutrophils protect against further thrombotic processes by clearing platelet and endothelial cell-remnants. In addition, this study shows that the different monocyte subsets are also involved in this process. Furthermore, both monocytes and neutrophils show increased TF expression in ACS.

Topics: Acute Coronary Syndrome; Acute Disease; Adult; Aged; Aged, 80 and over; Antigens, CD; Apoptosis; Blood Cells; Blood Coagulation; Cells, Cultured; Endothelial Cells; Female; Humans; Male; Middle Aged; Phagocytes; Phagocytosis; Thromboplastin; Young Adult

Topics: Acute Coronary Syndrome; Aged; Cell Membrane; Female; Humans; Male; Middle Aged; Thromboplastin

The aim of this study was to investigate the tissue factor (TF) expression of platelets and leukocytes in patients with acute coronary syndrome (ACS), patients with stable angina (SA) and healthy subjects (as controls). 26 patients with ACS, 29 patients with SA, and 25 controls were enrolled in this study. The peripheral blood samples of above-mentioned subjects were collected and isolated to obtain the monocytes and platelet-rich plasma, the TF-mRNA expression of monocytes, and platelets among 3 groups was detected by RT-PCR, the TF expression ratio of platelets, platelet-leukocyte aggregates (PLA) and platelet-monocyte aggregates (PMP) was detected by flow cytometry among 3 groups. The results showed that the TF mRNA expression level of platelets in ACS group were significantly higher (3.11 ± 0.51 relative expression) as compared with SA and control groups (1.88 ± 0.78 and 0.7 ± 0.1, respectively) (P = 0.03). Expression of TF mRNA of monocytes was higher in ACS group (P = 0.05 versus controls) too. ACS group had a significantly higher amount of TF-positive platelets (8.8 ± 2.6) than SA (2.6 ± 0.5, P = 0.02) or control groups (2.5 ± 0.4, P = 0.02). A significantly greater number of TF positive platelet-leukocyte aggregates and platelet-monocyte aggregates were also found by flow cytometry in blood of ACS patients than in either SA patients or controls. It is concluded that the high TF expression of platelets and leukocytes in ACS patients strengthens the platelet activation, blood coagulation, and thrombus formation and may further contribute to the hypercoagulability associated with the disease. The present study further extends the proinflammatory/prothrombotic phenotype of ACS patients showing that new players on the scene.

Topics: Acute Coronary Syndrome; Aged; Angina, Stable; Blood Platelets; Case-Control Studies; Cell Adhesion; Female; Humans; Leukocytes; Male; Middle Aged; Platelet Aggregation; RNA, Messenger; Thromboplastin

As microparticles are shedded upon platelet activation, and may be used to assess platelet function, we measured plasma concentrations of platelet-derived microparticles (PMPs) during and after an acute coronary syndrome (ACS). Fifty-one patients with ACS were investigated at admission, within 24 hours (before coronary angiography), and six months later. Sixty-one sex- and age-matched healthy controls were investigated once. PMPs were defined as particles <1.0 μm in size, negative to phalloidin (labels cell-fragments), and positive to CD61. Exposure of phosphatidylserine (PS+), CD62P and CD142 were also measured. Plasma concentrations of PS+PMPs exposing CD61, CD62P and CD142 were elevated 2.5, 6.0-, and 5.0-fold at admission (p<0.001 for all, compared to controls; aspirin only), decreased significantly 24 hours later following initiation of treatment with clopidogrel and subcutaneous anticoagulation (p<0.001 for all), and decreased even further six months later (p<0.01 for all). However, PS+PMPs exposing CD62P or CD142 were still between 1.2-and 2.3-fold higher than in controls (p<0.001 for both). The pattern for PS-PMPs during and after the ACS was very similar to that for PS+PMPs although the numbers were approximately 1/3 lower. In conclusion, PMP concentrations follow the pattern of platelet activation during and after an ACS. Decreased concentrations are observed after initiation of antithrombotic treatment, but PMP exposing CD62P or CD142 are still elevated after six months. Flow cytometric measurements of PMP in frozen-thawed samples enable studies of platelet function in larger clinical trials.

Topics: Acute Coronary Syndrome; Adult; Aged; Aged, 80 and over; Analysis of Variance; Anticoagulants; Biomarkers; Blood Platelets; C-Reactive Protein; Case-Control Studies; Cell-Derived Microparticles; Female; Fibrinogen; Fibrinolytic Agents; Flow Cytometry; Humans; Inflammation Mediators; Integrin beta3; Interleukin-6; Male; Middle Aged; P-Selectin; Particle Size; Phosphatidylserines; Platelet Activation; Platelet Aggregation Inhibitors; Sweden; Thromboplastin; Time Factors; von Willebrand Factor

The mechanisms responsible for increased cardiovascular risk associated with HIV-1 infection are incompletely defined. Using flow cytometry, in the present study, we examined activation phenotypes of monocyte subpopulations in patients with HIV-1 infection or acute coronary syndrome to find common cellular profiles. Nonclassic (CD14(+)CD16(++)) and intermediate (CD14(++)CD16(+)) monocytes are proportionally increased and express high levels of tissue factor and CD62P in HIV-1 infection. These proportions are related to viremia, T-cell activation, and plasma levels of IL-6. In vitro exposure of whole blood samples from uninfected control donors to lipopolysaccharide increased surface tissue factor expression on all monocyte subsets, but exposure to HIV-1 resulted in activation only of nonclassic monocytes. Remarkably, the profile of monocyte activation in uncontrolled HIV-1 disease mirrors that of acute coronary syndrome in uninfected persons. Therefore, drivers of immune activation and inflammation in HIV-1 disease may alter monocyte subpopulations and activation phenotype, contributing to a pro-atherothrombotic state that may drive cardiovascular risk in HIV-1 infection.

Topics: Acute Coronary Syndrome; Adult; Aged; Female; Flow Cytometry; HIV Infections; HIV-1; Host-Pathogen Interactions; Humans; Immunophenotyping; Interleukin-6; Lipopolysaccharide Receptors; Lipopolysaccharides; Male; Middle Aged; Monocytes; Receptors, IgG; Thromboplastin; Young Adult

Recent studies have suggested that circulating inflammatory cells augment the growth of thrombus in acute coronary syndrome (ACS). We therefore immunohistochemically analyzed thrombi in aspirates obtained from patients immediately after the onset of ACS.. Two hundred twenty samples were studied. Total thrombus area, white thrombus area, and red thrombus area were measured. As antibodies in immunohistochemical staining, myeloperoxidase (MPO), CD66b, CD68, p-selectin, tissue factor (TF) and PAI-1 were employed respectively.. The ratios of areas of red and white thrombi correlated with whole sample areas of enlarged thrombi (r = 0.48, p < 0.001). The immunohistochemical findings revealed granulocytes and macrophages aggregated around p-selectin-positive platelets that shared the boundary between white and red thrombi, a region where MPO and CD66b expression was abundant in neutrophils. The ratios (%) of MPO- and CD66b-positive cells significantly correlated with whole sample areas (r = 0.50; p < 0.001 and r = 0.49; p < 0.001, respectively). Neutrophils and macrophages within thrombi were positive for TF and PAI-1. Along the boundary between red and white thrombi, TF and PAI-1 positivity coincided with MPO-, CD66b- and CD68-positive cells. The ratios of cells positive for both TF and PAI-1 in this area significantly correlated with the whole sample area (r = 0.43, p < 0.001 and r = 0.60, p < 0.001, respectively).. These results suggested that enhanced activation of peripheral neutrophils together with increased TF and PAI-1 expression might comprise a considerable portion of thrombus enlargement.

Topics: Acute Coronary Syndrome; Acute Disease; Adult; Aged; Aged, 80 and over; Female; Humans; Immunohistochemistry; Inflammation Mediators; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Thromboplastin; Thrombosis

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Anticoagulants; CD40 Ligand; Heparin; Monocytes; Risk Factors; Thromboplastin

Adipocytes are nowadays recognised as cells able to produce and secrete a large variety of active substances termed adipokines, which exert direct effects on vascular cells. Among these adipokines, leptin has been proposed to play a role in the pathophysiology of acute coronary syndromes, as well as in increasing cardiovascular risk. At the moment, however, the mechanisms linking leptin to cardiovascular disease are not completely understood. This study investigates the effects of leptin, in a concentration range usually observed in the plasma of patients with increased cardiovascular risk or measurable in patients with acute coronary syndromes, on tissue factor (TF) and cellular adhesion molecules (CAMs) expression in human coronary endothelial cells (HCAECs). We demonstrate that leptin induces transcription of mRNA for TF and CAMs by real-time PCR. In addition, we show that this adipokine promotes surface expression of TF and CAMs that are functionally active since we observed increased procoagulant activity and leukocyte adhesion on cell surface. Leptin effects appear modulated by eNOS-production of oxygen free radicals through the activation of the transcription factor, nuclear factor(NF)-kappaB, since L-NAME, Superoxide Dismutase and NF-kappaB inhibitors suppressed CAMs and TF expression. Data of the present study, although in vitro , indicate that leptin may exert direct effects on human coronary endothelial cells by promoting CAMs and TF expression and support the hypothesis that this adipokines, besides being involved in the pathophysiology of obesity, might play a relevant role as an active mediator linking obesity to cardiovascular disease.

Topics: Acute Coronary Syndrome; Atherosclerosis; Cell Adhesion Molecules; Cells, Cultured; Coronary Thrombosis; Coronary Vessels; Endothelial Cells; Enzyme Inhibitors; Humans; Leptin; NF-kappa B; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase Type III; Reactive Oxygen Species; Thromboplastin

Serum C-reactive protein (CRP) is a strong risk predictor of cardiovascular events, and tissue factor (TF) plays a central role in thrombus formation of advanced atherosclerotic plaques. Aim of the present study was to quantify in situ CRP and TF in coronary atherectomy specimens associated with acute coronary syndromes (ACS) or stable angina (SA). In addition, the effect of statin treatment on both intimal determinants was analyzed.. Serial sections from atherectomy probes retrieved from coronary primary target lesions of 42 ACS and 70 SA patients were examined for CRP and TF expression using immunostaining. CRP and TF intimal expression was consistently higher in ACS lesions and a positive correlation between both determinants was detected. In both subgroups intimal staining intensity of CRP but not TF was strongly associated with serum CRP levels. Using angioscopy, complex plaques revealed a higher intimal CRP and TF expression than white/yellow plaques. Both CRP and TF were consistently lower expressed in target lesions of patients with pre-existing statin treatment.. CRP and TF expression is markedly increased in plaques derived from patients with ACS as compared to SA patients. Statin treatment appears to reduce vascular expression of CRP and TF.

Topics: Acute Coronary Syndrome; Aged; Angina Pectoris; Angioscopy; Atherectomy, Coronary; Atherosclerosis; C-Reactive Protein; Female; Gene Expression Regulation; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Thromboplastin; Thrombosis

Elevated serum amyloid A (SAA) levels, like C-reactive protein (CRP), predict coronary events. Both induce monocyte tissue factor (TF), and peripheral blood mononuclear cells (PBMC) from patients with coronary artery disease (CAD) express higher TF in response to CRP. This study examined SAA induction of TF and tumour necrosis factor-alpha (TNF) in PBMC from patients with CAD and in monocytoid THP-1 cells.. PBMC from 26 males with CAD (15 stable angina, SA, and 11 acute coronary syndromes, ACS) and 14 male controls were stimulated with SAA. SAA promoted up to six-fold increase in TF activity (recalcification assay) on PBMC from patients, associated with elevated TF mRNA and protein. PBMC responded optimally when monocytes were adherent. Unlike CRP, SAA induced TF and TNF in THP-1 cells. SAA-induced TNF was dose-dependently inhibited by HDL. PBMC from patients with ACS expressed more basal TF (257.4+/-46.8 mU/10(6) PBMC vs. 131.0+/-12.5 mU/10(6) PBMC, P=0.003), and greater SAA-induced TF than cells from controls, whereas no difference was found between SA and controls (ACS 2246+/-493, SA 1364+/-206, controls 1091+/-113 mU/10(6) PBMC, with SAA 250 ng/mL, P=0.002 ACS vs. controls across the dose range). Importantly, SAA-induced TNF levels (ELISA) were much higher in patients with ACS than SA or controls (ACS 211+/-41, SA 108+/-16, controls 73+/-11 pg/mL, with SAA 250 ng/mL, P=0.001 ACS vs. controls or P=0.013 ACS vs. SA across the dose range). SAA-induced TF and TNF correlated positively with serum SAA levels in CAD, but not controls.. SAA is a prothrombotic and proinflammatory mediator in ACS which may contribute to atherogenesis and its complications.

Topics: Acute Coronary Syndrome; Aged; Angina Pectoris; C-Reactive Protein; Cell Line; Cells, Cultured; Cholesterol, HDL; Humans; Leukocytes, Mononuclear; Male; Middle Aged; RNA, Messenger; Serum Amyloid A Protein; Thromboplastin; Thrombosis; Tumor Necrosis Factor-alpha; Vasculitis

Tissue factor (TF) is a main initiator of coagulation cascade. Its determination in conditions of acute coronary syndrome is logistically difficult. Hence, in our study, the activity and the concentration of TF and the count of microparticles in the platelet free plasma (PFP) were determined.. Blood was drawn from both coronary sinus and femoral vein circulation in a cohort of 40 patients. TF activity was measured by activation of factor X in the presence of factor VIIa, whereas microparticles were detected using flow cytometry. TF antigen concentrations were determined using the ELISA test.. TF activity in the stable angina subgroup was not significantly different from the control group (18.12 +/- 3.35 mOD/min vs. 17.72 +/- 4.05 mOD/min, respectively), but it was significantly lower in the unstable angina (7.62 +/- 4.19 mOD/min) and myocardial infarction (MI) (3.56 +/- 3.85 mOD/min) subgroups (P < 0.05). Results from the coronary sinus and femoral vein circulations were not significantly different. The count of microparticles decreased according to the severity of the acute coronary syndrome: control group, 520 +/- 172; stable angina subgroup, 532 +/- 167; unstable angina subgroup, 392 +/- 142; and MI subgroup, 165 +/- 30 (P < 0.05). There were no significant differences in concentrations of TF antigen in four subgroups.. These results suggest that the procoagulant TF-bearing microparticles could be recruited from PFP by interaction with platelets and blood cells in the conditions of acute coronary syndrome.

Topics: Acute Coronary Syndrome; Aged; Autoantigens; Blood Platelets; Cohort Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Pilot Projects; Prospective Studies; Thromboplastin

Enhanced expression of tissue factor (TF) may result in thrombosis contributing to acute clinical consequences of coronary artery disease. Several studies demonstrated elevated plasma levels of TF in patients with acute coronary syndrome (ACS). The aim of our study was to compare the concentrations of TF in coronary sinus (CS), proximal part of the left coronary artery (LCA) and peripheral vein (PV) of patients with ACS and stable coronary artery disease (SCAD). Time course of the TF plasma levels in PV was followed on day 1 and day 7 after index event of ACS presentation and was compared to day 0 values. No heparin was given prior to the blood sampling. Twenty-nine patients in the ACS group (age 63.6+/-10.8 years, 20 males, 9 females) and 24 patients with SCAD (age 62.3+/-8.1 years, 21 males, 3 females) were examined. TF plasma level was significantly higher in patients with ACS than in those with SCAD (239.0+/-99.3 ng/ml vs. 164.3+/-114.2 ng/ml; p=0.016). There was no difference in TF plasma levels in PV, CS and LCA (239.0+/-99.3 ng/ml vs. 253.7+/-131.5 ng/ml vs. 250.6+/-116.4 ng/ml, respectively). TF plasma levels tended to decrease only non-significantly on the day 7 (224.4+/-109.8 ng/ml). Significant linear correlation between TF and high sensitivity CRP (hs-CRP) levels on day 0 was found. In conclusion, TF plasma levels are elevated in patients with ACS not only locally in CS but also in systematic circulation. Our data support the relationship between TF production and proinflammatory mediators.

Topics: Acute Coronary Syndrome; Aged; Coronary Artery Disease; Coronary Sinus; Female; Humans; Male; Middle Aged; Thromboplastin

Asymmetric dimethylarginine (ADMA), a major endogenous inhibitor of nitric oxide synthase, is recently defined as an independent cardiovascular risk factor. Tissue factor (TF) expression and procoagulant activity (PCA) of peripheral monocytes are increased in patients with acute coronary syndromes (ACS), which resulted in blood procoagulant state tending to thrombus formation. In the present study, we tested the hypothesis that ADMA contribute to TF expression of peripheral monocytes in ACS. Twenty patients with unstable angina (UA), 20 patients with stable angina (SA) and 20 control subjects were recruited. Monocytic cell line THP-1 was incubated with different concentrations of ADMA (1-10microM) for various periods (6-24h). Our results showed that plasma level of ADMA in patients with UA was significantly higher than those in patients with SA or in the control group, and positively correlated with TF antigen level and PCA of circulating monocytes. Adjusting for all patient characteristics, we confirmed these findings in multivariate regression analyses. In cultured THP-1 cells, ADMA transcriptionally upregulated both TF antigen expression and PCA in a concentration-dependent manner. The experiments using nuclear factor-kappaB (NF-kappaB) inhibitor and transient transfection with wild-type and mutated TF promotor constructs showed that the NF-kappaB is an important transcriptional regulator of ADMA-induced TF expression. Our results suggest that elevated plasma level of ADMA induces TF expression in monocytes via NF-kappaB-dependent pathway, which contributes to procoagulant phenotype of circulating monocytes in ACS.

Topics: Acute Coronary Syndrome; Aged; Angina Pectoris; Arginine; Blood Coagulation; Case-Control Studies; Coagulants; Female; Humans; Male; Middle Aged; Monocytes; NF-kappa B; Nitric Oxide Synthase; Thromboplastin

It has been established that inflammation and enhanced pro-coagulant activity are associated with the pathogenesis of atherosclerotic vascular disease. We evaluated and compared the contributions of the factor (F)XIa and tissue factor (TF) activity in plasma of patients with coronary artery disease (CAD). Citrate plasma was obtained prior to therapy from 53 patients with stable angina (29 with a history of previous myocardial infarction; CAD-MI) and 30 with acute coronary syndrome (ACS) within 12 hours from pain onset. Four ACS patients treated with heparin were excluded. FXIa and TF activity were determined in clotting assays based upon the prolongation of clotting time by inhibitory monoclonal antibodies. Twenty-five of 26ACS patients (96%) and 22 of 29 CAD-MI patients (76%) had quantifiable FXIa (50 +/- 33 and 42 +/- 45pM, respectively). Ten of 26 (38%) ACS patients and only three of 53 (6%) stable CAD patients showed TF activity (<0.4pM). No FXIa or TF activity was observed in age-matched healthy controls (n = 12). For both CAD-MI and ACS patients, there were correlations (p < 0.05) between FXIa and interleukin-6 (R(2) = 0.59 and 0.39, respectively) and between FXIa and TAT (R(2) = 0.64 and 0.63, respectively). In conclusion, the majority of ACS and CAD-MI patients have circulating FXIa that correlates with markers of coagulation and inflammation.

Topics: Acute Coronary Syndrome; Aged; Angina Pectoris; Antithrombin III; Biomarkers; Blood Coagulation; Blood Coagulation Tests; Case-Control Studies; Coronary Artery Disease; Factor Xa; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Myocardial Infarction; Peptide Hydrolases; Thromboplastin

Activated platelets and circulating platelet-leukocyte aggregates (PLA) are significantly higher in patients with unstable angina than in those with stable angina (SA). Platelets from healthy subjects express TF on activation. The aim of this study was to investigate the expression of TF in PLA, in platelets, and in monocytes of acute coronary syndrome (ACS) patients compared to SA patients and healthy subjects (Controls).. We enrolled 26 consecutive patients with ACS, 29 patients with SA, and 25 Controls. A significantly greater number of total and TF positive platelet-monocyte aggregates was found by flow cytometry in blood of ACS patients than in either SA patients (3-fold) or Controls (5-fold). ACS patients also had a significantly higher amount of TF-positive platelets than SA or Controls (>3-fold) and significantly higher thrombin generation capacity. TF mRNA expression in platelets was significantly higher in ACS patients than in SA or Controls.. In ACS patients the greater expression of TF in platelets and PLA strengthens the link between platelet activation, blood coagulation, and thrombus formation and may further contribute to the hypercoagulability associated with the disease.

Topics: Acute Coronary Syndrome; Aged; Blood Coagulation; Blood Platelets; Case-Control Studies; Cell Aggregation; Female; Humans; Leukocytes; Male; Middle Aged; P-Selectin; Platelet Activation; RNA, Messenger; Thrombin; Thromboplastin; Thrombosis

Tissue factor (TF) is a low-molecular-weight glycoprotein responsible for the initiation of the coagulation cascade. The relation between oxidized low-density lipoprotein (Ox-LDL), that has been shown to be involved in atherogenesis, and TF has not been evaluated before in circulating plasma. The aim of this study was to determine plasma levels of TF and Ox-LDL in acute coronary syndrome (ACS) and stable coronary artery disease (SCAD).. The study group consisted of 41 patients with ACS and 26 patients with SCAD. Among the ACS patients, 12 were diagnosed with unstable angina pectoris (UAP) and 29 were diagnosed with acute myocardial infarction (AMI). The control group consisted of 30 healthy volunteers. TF and Ox-LDL levels were evaluated by ELISA kits.. Ox-LDL levels were significantly higher in UAP and AMI patients compared with the control (p < 0.001) and SCAD (p < 0.01 and p < 0.001, respectively) groups. TF levels were significantly higher in the UAP, AMI and SCAD groups compared with the control group (p < 0.001, p < 0.001 and p < 0.01, respectively). In the AMI group a significant increase was observed in TF levels when compared with the SCAD group (p < 0.01). Plasma Ox-LDL levels were significantly and positively correlated with TF levels in the UAP and AMI groups (p < 0.05, r = 702, and p < 0.0001, r = 0.679, respectively).. The potential link between Ox-LDL and TF in circulating blood in ACS may strengthen the evidence supporting a relationship between oxidant stress, lipids and thrombosis and consequently may contribute to understanding the mechanism through which Ox-LDL and TF may mediate the pathogenesis of CAD.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Angina, Unstable; Blood Coagulation; Enzyme-Linked Immunosorbent Assay; Female; Humans; Lipoproteins, LDL; Male; Middle Aged; Myocardial Infarction; Oxidative Stress; Thromboplastin