Hyperlipidemia and in vivo Hemostatic System Activation

Owen, John; Grossman, Betty A.; Palmer, Robert L.

doi:10.1055/s-2007-1002784

Cited by 10 publications

(3 citation statements)

References 18 publications

(18 reference statements)

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“…Previous work in our laboratory has shown that monocytederived macrophages from the pigeon bind fibrinogen and express glycoproteins IIb and IIIa, which are components of the fibrino-gen receptor in both mammalian platelets and avian thrombocytes (22,23).Conceivably, the monocyte related fibrinogen binding is related to procoagulant activity, for in this study, we have documented an increased production of tissue factor by activated monocytes/macrophages. Various studies (38)(39)(40)(41) have linked macrophage activation with thrombosis, the major pathogenic sequelae to atherosclerosis. Monocyte-derived macrophages are hallmarks of atherosclerosis and are consistently present in advanced lesions.…”

Section: Discussionmentioning

confidence: 99%

Expression and Localization of Tissue Factor-Based Procoagulant Activity (PCA) in Pigeon Monocyte-Derived Macrophages

Gupta

Doellgast

Cheng³

et al. 1993

Thromb Haemost

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SummaryMonocyte-derived macrophages, focal to initiation and progression of atherosclerosis, have been implicated in thrombotic complication of this disease. In the present study we demonstrated tissue factor based procoagulant activity in cultured macrophages from the White Carneau pigeon following endotoxin (1-2 μg/ml) stimulation. This macrophage procoagulant activity paralleled activity obtained with pigeon brain homogenate. We used Enzyme-Linked Coagulation Assay (ELCA), an ultrasensitive microtiter plate assay, to measure procoagulant activity in these cells. Through the use of clotting factors purified from pigeon plasma, procoagulant activity could be detected with as few as 1-3 cells. Tissue factor antigen, detected through the use of immunogold labelling in conjunction with a polyclonal antibody which was highly specific to human tissue factor, was distributed uniformly over the plasma membrane of the endotoxin-stimulated cells. These studies suggest that this procoagulant activity might play an important role in the pathobiology of atherosclerosis in White Carneau pigeons by initiating fibrin polymerization and thus leading to thrombotic complications of the disease.

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Section: Discussionmentioning

confidence: 99%

Expression and Localization of Tissue Factor-Based Procoagulant Activity (PCA) in Pigeon Monocyte-Derived Macrophages

Gupta

Doellgast

Cheng³

et al. 1993

Thromb Haemost

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“…Human K-thrombin was produced by activating prothrombin with taipan-snake venom [14,15]. Activated K-thrombin was assayed by measuring its amidolytic activity towards a chromogenic substrate and puri¢ed by taking advantage of its highly speci¢c a¤nity to heparin, which was immobilised on a matrix support of sepharose [16].…”

Section: Crystallisationmentioning

confidence: 99%

X‐ray and spectrophotometric studies of the binding of proflavin to the S1 specificity pocket of human α‐thrombin

Conti

Rivetti

Wonacott³

et al. 1998

FEBS Letters

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Proflavin can be used to study the interactions of inhibitors and substrates with thrombin by monitoring the changes in the visible absorption spectrum that occur on dye displacement. We have used microspectrophotometric methods to investigate the binding of proflavin to crystals of an K K-thrombinhirugen complex and have determined the structure by X-ray crystallography. The proflavin molecule binds in the S1 pocket of the enzyme with one of the amino groups hydrogen bonded to the carboxylate of Asp-189 while the protonated ring nitrogen is hydrogen bonded to the carbonyl of Gly-219. This result indicates that the proflavin displacement assay can be used to specifically monitor the binding of inhibitors to the S1 pocket.z 1998 Federation of European Biochemical Societies.

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“…The most documented pathologies in this field concern hyperlipidemia, hypertrigl~cericl~rnia, and diabetes. Each disease has its own effect on coagulolytic equilibrium (14). Lipid anomalies produce endothelial modifications (atherosclerosis) and factors XII and VII ac-TABLE 3.…”

Section: Presently Available Molecular Markersmentioning

confidence: 99%

State-of-the-Art Review: Molecular Markers in Thrombosis and Hemostasis

Amiral¹

1997

Clin Appl Thromb Hemost

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Molecular markers for exploring the different stages of hemostasis activation are now available. These markers allow investigation of endothelial functions, blood cell activation, stimulation of coagulation pathways, involvement of the fibrinolytic system, and profiling of the coagulolytic-equilibrium that regulates hemostasis. Additionally, these markers find useful applications for monitoring therapies, following-up clinical states associated with high thrombotic risk, and validating new drugs and analyzing their mode of action. Furthermore, these markers may allow for recognition of the evolution of early disease in the clinically silent phase. Large scale epidemiological and longitudinal studies are required for establishing this latter approach. Up to now, only D. Dimer is used in routine clinical application for exclusion diagnosis of deep-veinous-thrombosis and pulmonary embolism. Other markers must prove their sensitivity for the early asymptomatic period and demonstrate their applicability throughout disease evolution. According to pathology and application, different markers may provide complementary information. Some markers, e.g., D.Dimer, soluble thrombomodulin, and modified AT-III (ATM), are used on standard citrated plasma samples. Modem and flexible technologies are now available for point-of-care testing (when required), quick and sensitive measurements in emergency conditions, and full automation when necessary. Lastly, factors that trigger hemostatic activation can now be evaluated and provide information on etiology. In this latter respect, autoimmunity may be important in thrombotic disease induction.A major unresolved question concerns the evaluation of the activation state of blood and vascularture. Finding an answer would have multiple applications in following evolution of clinical states; evaluating the antithrombotic efficacy of anticoagulant, antithrombotic, and thrombolytic therapies (and, therefore, adjusting the drug dosage and/or establishing the correct therapeutic strategy); and identifying patients who present the highest thrombotic risk in clinical states frequently associated with this complications (1). Furthermore, the ability to evaluate the activation state of blood and vasculature could lead to preventive measures for the general population, and ~i~'er the possibility of selecting individuals in the early stage of disease ~w~-' lution and provide them with appropriate therapy (2). However, applications for the many proposed indicators of blood activation, originating from plasma factors, blood cells, or endothelial stimulation, are still mainly restricted to highly specialized research studies. The reasons for this are multiple and concern the molecular markers themselves as well as the assay methods used for their measurement. Actually, most of these molecular markers are present at very low concentrations, are frequently generated only in the symptomatic period, present usually with very short half-lives, and are ' very often sensitive to ex vivo blood activation, which...

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Hyperlipidemia and in vivo Hemostatic System Activation

Cited by 10 publications

References 18 publications

Expression and Localization of Tissue Factor-Based Procoagulant Activity (PCA) in Pigeon Monocyte-Derived Macrophages

Expression and Localization of Tissue Factor-Based Procoagulant Activity (PCA) in Pigeon Monocyte-Derived Macrophages

X‐ray and spectrophotometric studies of the binding of proflavin to the S1 specificity pocket of human α‐thrombin

State-of-the-Art Review: Molecular Markers in Thrombosis and Hemostasis

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