P-Selectin–Dependent Inhibition of Thrombosis During Venous Stasis

Eppihimer, Michael J.; Schaub, Robert G.

doi:10.1161/01.atv.20.11.2483

Cited by 69 publications

(53 citation statements)

References 40 publications

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“…Although endothelial disruption is characteristic, it is often less extensive than that which triggers arterial thrombosis. 49 Additionally, leukocyte adhesion and transmigration have been demonstrated as early events in the initiation of venous thrombosis. 49,50 Thus, it has been proposed that circulating TF, perhaps derived from leukocytes, could be a key determinant of fibrin generation in this setting.…”

Section: Discussionmentioning

confidence: 99%

“…49 Additionally, leukocyte adhesion and transmigration have been demonstrated as early events in the initiation of venous thrombosis. 49,50 Thus, it has been proposed that circulating TF, perhaps derived from leukocytes, could be a key determinant of fibrin generation in this setting. 38,51 Interestingly, a recent study demonstrated that inhibition of TF significantly reduced fibrin accumulation on a collagen-coated thread implanted into a rabbit vein.…”

Section: Discussionmentioning

confidence: 99%

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Macrovascular thrombosis is driven by tissue factor derived primarily from the blood vessel wall

Day

Reeve

Pedersen

et al. 2005

Blood

261

227

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Leukocytes and leukocyte-derived micro-particles contain low levels of tissue factor (TF) and incorporate into forming thrombi. Although this circulating pool of TF has been proposed to play a key role in thrombosis, its functional significance relative to that of vascular wall TF is poorly defined. We tested the hypothesis that leukocyte-derived TF contributes to thrombus formation in vivo. Compared to wild-type mice, mice with severe TF deficiency (ie, TF / , hTF-Tg , or "low-TF") demonstrated markedly impaired throm-bus formation after carotid artery injury or inferior vena cava ligation. A bone marrow transplantation strategy was used to modulate levels of leukocyte-derived TF. Transplantation of low-TF marrow into wild-type mice did not suppress arterial or venous thrombus formation. Similarly, transplantation of wild-type marrow into low-TF mice did not accelerate thrombosis. In vitro analyses revealed that TF activity in the blood was very low and was markedly exceeded by that present in the vessel wall. Therefore, our results suggest that thrombus formation in the arterial and venous macrovasculature is driven primarily by TF derived from the blood vessel wall as opposed to leuko-cytes. (Blood. 2005;105:192-198)

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Macrovascular thrombosis is driven by tissue factor derived primarily from the blood vessel wall

Day

Reeve

Pedersen

et al. 2005

Blood

261

227

View full text Add to dashboard Cite

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“…This process is dependent upon selectins, including P-selectin [14,15]. Genetic deficiency or pharmacological inhibition of P-selectin reduces thrombus formation across species [10,15,16]. P-selectin is released from Weibel-Palade bodies following endothelial activation [17,18].…”

Section: Dissecting the Early Phase Of Venous Thrombus Formationmentioning

confidence: 99%

Crossroads of coagulation and innate immunity: the case of deep vein thrombosis

Schulz

Engelmann

Maßberg

2013

Journal of Thrombosis and Haemostasis

105

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Summary Deep vein thrombosis (DVT) is a common condition characterized by the formation of an occlusive blood clot in the venous vascular system, potentially complicated by detachment and embolization of thrombi into the lung. Recent evidence from mouse models has shed light on the sequence of events and on the cellular (innate immune cells, platelets) and molecular (hematopoietic tissue factor, nucleic acids) components involved. In response to decreased blood flow, circulating neutrophils and monocytes adhere to the activated endothelium within hours. They initiate and propagate DVT by interacting with platelets and by the exposure and activation of circulating tissue factor and FXII. Intravascular blood coagulation is also induced by extracellular nucleosomes released mainly from activated neutrophils. Interestingly, these mechanisms are closely linked to an evolutionary conserved immune defense mechanism activated in response to infections. In this review, we will give an overview of DVT and the role of innate immune pathways supporting this process. While the latter are aimed at preserving tissue integrity and function, uncontrolled blood coagulation and activation of immune cells may result in pathological thrombus formation and vascular occlusion. Understanding the molecular and cellular players triggering occlusion of large veins, and their distinction from physiological hemostasis, is important for the development of strategies to prevent and treat DVT.

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“…One consequence is the inhibition of the interaction between P-selectin and its receptor, which occurs on different cell types, including platelets and leukocytes. Inhibiting the interaction between P-selectin and PSGL-1 with P-selectin antagonists (recombinant soluble PSGL-immunoglobulin), intravenously administered soluble ligands, or an orally administered nonprotein inhibitor (PSI-697) markedly attenuated the prothrombotic effect in a mouse model (13)(14)(15)(16)(17). Statin medication has recently been reported to reduce sP-selectin concentrations significantly (38 -40 ), and sP-selectin concentration was inversely correlated with the progression of coronary heart disease (38 ).…”

Section: /97mentioning

confidence: 99%

High Concentrations of Soluble P-Selectin Are Associated with Risk of Venous Thromboembolism and the P-Selectin Thr715 Variant

Ay¹,

Jungbauer²,

Sailer³

et al. 2007

Clinical Chemistry

116

109

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Background:The cell adhesion molecule P-selectin has an important role in the pathophysiology of thrombosis. The effect on venous thromboembolism (VTE) of increased circulating concentrations of soluble P-selectin (sP-selectin) and their association with the P-selectin variant Thr715Pro is still uncertain. Methods: This study was a case-control study of 116 patients with confirmed recurrent VTE and at least 1 event of unprovoked deep venous thrombosis or pulmonary embolism, and 129 age-and sex-matched healthy individuals. We measured sP-selectin by ELISA and P-selectin gene (SELP) variation by genotyping and sampled blood after a mean interval of 2.55 years after the most recent VTE event. Results: The mean (SD) sP-selectin concentration was higher in patients than in controls: 47.3 (15.0) g/L vs 36.8 (11.0) g/L, P <0.001. The unadjusted odds ratio (OR) for sP-selectin >55.1 g/L, representing the 95th percentile for controls, was 8.5 (95% CI, 3.7-23.3; P <0.001) and increased after adjustment for factor V Leiden, the prothrombin G20210A variant, increased factor VIII, and hyperhomocysteinemia (OR, 10.6; 95% CI, 4.1-31.2; P <0.001). Pro715 carriers were more prevalent among controls than patients (21.7% vs 14.7%).

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P-Selectin–Dependent Inhibition of Thrombosis During Venous Stasis

Cited by 69 publications

References 40 publications

Macrovascular thrombosis is driven by tissue factor derived primarily from the blood vessel wall

Macrovascular thrombosis is driven by tissue factor derived primarily from the blood vessel wall

Crossroads of coagulation and innate immunity: the case of deep vein thrombosis

High Concentrations of Soluble P-Selectin Are Associated with Risk of Venous Thromboembolism and the P-Selectin Thr715 Variant

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