Pathogenesis of venous thrombosis: a new insight

Wakefield, Thomas W.; Strieter, Robert M.; Prince, Martin R.; Downing, L.; Greenfield, Lazar J.

doi:10.1016/s0967-2109(96)00083-x

Cited by 77 publications

(47 citation statements)

References 84 publications

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“…For instance, the proinflammatory properties of vein endothelium likely influence the development of venous thrombosis and vein graft atherosclerosis in which inflammatory responses play major roles. 7,12,14,16 In parallel, the development of thromboembolic complications in diseases such as infections, inflammatory disease, or malignancy may be influenced by the reactive venous endothelium that can respond to systemic inflammatory stimuli released in these syndromes. Such notion is supported by our data in which strong adhesion of leukocytes was induced by intravenous treatment with TNF-␣.…”

Section: Discussionmentioning

confidence: 99%

Powerful Inflammatory Properties of Large Vein Endothelium In Vivo

Eriksson

Karlöf

Lundmark

et al. 2005

ATVB

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Objective-Inflammatory responses of large vein endothelium are of importance in pathological processes such as venous thrombosis, chronic venous congestion, and vein graft atherosclerosis. However, the inflammatory properties of large vein endothelium are unclear. Methods and Results-In this study, we used several microscopy techniques to investigate the inflammatory properties of large vein endothelium in vivo. We show that the endothelium in the mouse inferior vena cava (IVC) possesses powerful inflammatory properties that are distinct from the less inflammatory reactive aortic endothelium and virtually identical to endothelial responses in postcapillary venules. Inflammatory stimulation with tumor necrosis factor-␣ induced strong expression of cell adhesion molecules (CAMs) in the IVC. These CAMs promoted recruitment of leukocytes, platelets, and erythrocytes to the vein wall. The inflammatory responses altered endothelial structure and increased endothelial permeability in the IVC. Accumulation of blood cells and endothelial damage were markedly reduced in mice deficient in the endothelial leukocyte recruitment molecules E-selectin and P-selectin, indicating a central role for these molecules in driving structural and functional changes of IVC endothelium. Key Words: endothelium Ⅲ leukocyte Ⅲ rolling Ⅲ adhesion Ⅲ vein Ⅲ inflammation T he vascular endothelium functions as a barrier between tissue and blood and regulates diverse functions such as local and central hemodynamics, exchange of nutrients and metabolites, hemostasis, and immunity. [1][2][3] The endothelium also plays important roles in inflammatory diseases, atherosclerosis, and thrombosis. 4 -7 The endothelial monolayer is a diverse family of cells that, depending on the location in the vascular tree, displays variable responses to a variety of stimuli. For instance, endothelial phenotype in arteries is characterized by the release of substances that influence vascular smooth muscle tone, vessel diameter, and local blood perfusion. 8 Endothelium in postcapillary venules, on the other hand, is specialized at responding to local inflammatory stimuli by increasing its permeability toward macromolecules and by expression of molecules that mediate recruitment of leukocytes to sites of inflammation. 9 The factors that guide endothelial cell phenotype are not fully understood. However, endothelial function is influenced by the developmental origin of the cells as well as by local blood flow dynamics. 10,11 In contrast to the endothelium in arteries and venules, little is known about endothelial function in large veins. Nonetheless, the responses of large vein endothelium play important roles in clinical disease. For example, accumulation of leukocytes on venous endothelium is important in the initial stages of thrombosis. 12 Moreover, destruction of venous valves leading to chronic venous congestion is imposed by inflammatory mechanisms. 13 Furthermore, veins grafted into the arterial circulation in bypass surgery rapidly develop vein graft atherosclero...

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Section: Discussionmentioning

confidence: 99%

Powerful Inflammatory Properties of Large Vein Endothelium In Vivo

Eriksson

Karlöf

Lundmark

et al. 2005

ATVB

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“…34 Platelet adhesion to neutrophils facilitates the production of superoxide, 35,36 thromboxane, 37 leukotriene C 4 , 37 and platelet activating factor. 38 Inhibition of leukocyteplatelet adhesion with a P-selectin mAb significantly reduced the production of thromboxane and leukotriene C 4 . 37 Several studies have demonstrated that neutrophils can inhibit platelet aggregation and function by the release of products such as elastase 39 and NO-like 40 and endothelium-derived relaxing factor-like 41 factors.…”

Section: Discussionmentioning

confidence: 99%

P-Selectin–Dependent Inhibition of Thrombosis During Venous Stasis

Eppihimer¹,

Schaub²

2000

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Abstract-Leukocyte adhesion, transendothelial migration, and stasis are important components in the pathogenesis of deep vein thrombosis. Anesthetized cats were treated with saline, a recombinant soluble form of P-selectin glycoprotein ligand-1 (rPSGL-Ig), or an E-and L-selectin antibody (EL-246) before exposure and occlusion of a jugular vein. After 2 or 6 hours of occlusion, jugular veins were perfused with buffer, fixed, and prepared for scanning electron microscopy. In cats receiving saline, 2 and 6 hours of occlusion produced moderate levels of leukocyte and platelet adhesion and endothelial cell injury. Treatment of cats with rPSGL-Ig or EL-246 had no apparent effect on the magnitude of cell adhesion and endothelial cell injury compared with no treatment. After 6 hours of occlusion, the presence of a mural thrombus in untreated veins was observed and confirmed by scanning electron microscopy. Pretreatment of cats with rPSGL-Ig completely (4.0 mg/kg) or partially (1.0 mg/kg) prevented the occurrence of thrombi in the jugular veins. The reduction in thrombosis by rPSGL-Ig treatment after 6 hours of venous stasis, in the absence of any effect on leukocyte-mediated endothelial cell injury, suggests an antithrombotic mechanism of action for this protein.

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“…Another limitation is that comparison between the two clots requires an internal standard with the same hardness in both images, as it is difficult to know the force that was used to deform the tissue in each case. Rubin et al used the wall of the vein as standard but the hardness difference estimate was conservative due to lack of another standard reference (31). Another limitation is that it is difficult to distinguish between subacute and chronic thrombi that are closer in age (29).…”

Section: Sonographic Elasticity Imaging (Sei)mentioning

confidence: 99%