Thromboxane A(2) (TXA(2)) synthesis and expression of procoagulant activity (PCA) were investigated in mononuclear cells and monocytes prepared from a control and a Type 2 diabetic group. Monocytes from the diabetic group produced 2.10+/-0.81 ng of TXB(2)/5 x 10(5) monocytes compared to 1.26+/-0.43 ng/5 x 10(5) monocytes by the control group (P<0.01, n=11) when incubated in autologous plasma containing arachidonic acid (200 microg/ml). When monocytes were incubated in buffer containing arachidonic acid (20 microg/ml), cells from the diabetic group produced 1.65+/-0.68 ng of TXB(2)/5 x 10(5) monocytes compared to 1.07+/-0.31 ng/5 x 10(5) monocytes by the control group (P<0.02, n=12). Expression of PCA was examined in mononuclear cell preparations. Basal and maximally stimulated PCA with lipopolysaccharide (4.2 microg/ml) were not different between control and diabetic groups. However, arachidonic acid induced a four-fold (P<0.001) increase in PCA in the diabetic group. This activity was characterized as tissue factor. Increased synthesis of TXA(2) and expression of PCA may potentiate thrombosis and increase fibrin deposition, events that play primary roles in the development of vascular disease.
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http://dx.doi.org/10.1054/plef.2001.0301 | DOI Listing |
J Thromb Haemost
January 2025
Case Western Reserve University, School of Medicine, Department of Pharmacology, Cleveland, OH United States. Electronic address:
Background: Hypercoagulation and thrombin generation are major risk factors for venous thrombosis. Sustained thrombin signaling through PAR4 promotes platelet activation, phosphatidylserine exposure, and subsequent thrombin generation. A single-nucleotide polymorphism in PAR4 (rs2227376) changes proline to leucine extracellular loop 3 (P310L), which decreases PAR4 reactivity and is associated with a lower risk for venous thromboembolism (VTE) in a GWAS meta-analysis.
View Article and Find Full Text PDFThromb Res
December 2024
Department of Obstetrics and Gynaecology, Trinity College Dublin, Dublin, Ireland; Trinity St. James's Cancer Institute, Dublin, Ireland. Electronic address:
Background: Tumour type, treatment and patient related factors contribute to cancer associated venous thromboembolism (VTE), however, the role of each factor and the mechanisms involved are not understood.
Aim: To assess the role of the tumour, and of chemotherapy, in mediating the procoagulant response associated with VTE in gynaecological cancer patients.
Methods: Gynaecological cancer patients who developed VTE during follow-up (n = 59) (VTE+) were matched with treatment naïve(treatment (-)(VTE-)(n = 120) and chemotherapy treated patients(treatment (+)(VTE-) (n = 57)).
Front Immunol
January 2025
Department of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, United States.
Sickle cell disease (SCD) is a devastating hemolytic disease, marked by recurring bouts of painful vaso-occlusion, leading to tissue damage from ischemia/reperfusion pathophysiology. Central to this process are oxidative stress, endothelial cell activation, inflammation, and vascular dysfunction. The endothelium exhibits a pro-inflammatory, pro-coagulant, and enhanced permeability phenotype.
View Article and Find Full Text PDFInflammation
December 2024
Department for Biomedical Research, University of Bern, Bern, Switzerland.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with systemic inflammation and vascular injury, which contribute to the development of acute respiratory syndrome (ARDS) and the mortality of COVID-19 infection. Moreover, multiorgan complications due to persistent endothelial dysfunction have been suspected as the cause of post-acute sequelae of SARS-CoV-2 infection. Therefore, elucidation of the vascular inflammatory effect of SARS-CoV-2 will increase our understanding of how endothelial cells (ECs) contribute to the short- and long-term consequences of SARS-CoV-2 infection.
View Article and Find Full Text PDFJ Thromb Haemost
December 2024
Institute of Vascular Biology and Thrombosis Research, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria. Electronic address:
Background: Platelets are pivotal in maintaining vascular integrity, hemostasis, and immune modulation, with newly generated, immature platelets being the most responsive in fulfilling these tasks. Therefore, the immature platelet fraction provides insights into thrombopoiesis dynamics and clinical prognostication. However, it is currently unclear how immature platelet functions change in settings of acute thrombocytopenia.
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