Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Microvessels of rat mesentery were used for the study. Proteins marked with fluorescent dyes are first visible in the vascular terminations. After 10 minutes they pass into the perivascular tissues where very fine reticular structures appear. The passage begins at the level of the venules, and continues in the interstitial tissue in the form of fibrils; the extravasation does not have a diffuse character (this has also been verified by other techniques). The ultraviolet microscope permits localization of the proteins because of their specific absorption. These experiments were conducted with labelled fibrinogen. Fibrinogen showed a high degree of selective affinity for the vessel wall, especially for that of the venules, and much less or none at all for that of the arterioles or the capillary loops. Fibrinogen is also found in the interstitial spaces and in the lymphatic vessels. The deposits in the vessel walls occur with a normal speed of blood flow. These intravenous deposit may be prevented by means of a preliminary injection of heparin. On the other hand they are very marked after inhibition of fibrinolysis by epsilon-aminocaproic acid and also by the addition of small doses of thrombin.
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PMID:[Exchanges of proteins, especially fibrinogen, between blood and lymph]. 90 33

The interaction of blood-borne lymphocytes with blood vascular endothelial cells is a fundamental component of lymphocyte circulation. The role of lymphatic endothelial cells is less certain. These studies describe the isolation, characterization and lymphocyte binding capacity of efferent lymphatic endothelial cells from ovine mesenteric lymphatic vessels. Lymphatic endothelial cells had anti-thrombin 3, von Willebrand Factor and MHC I on their surface. The cells also actively metabolized acetylated low density lipoprotein. The morphological appearance was indistinguishable from blood vascular endothelium but quite different from cultured smooth muscle cells. Lymphocyte binding to lymphatic endothelial cells was not significantly different from binding to carotid artery or jugular vein endothelial cells. The degree of binding in all cases could be enhanced by incubating endothelial cells in medium containing rh TNF-alpha (recombinant human tumor necrosis factor alpha).
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PMID:Characterization of ovine lymphatic endothelial cells and their interactions with lymphocytes. 820 71

The possibility of formation of lymphatic vessels after introduction of autologous bone marrow-derived multipotent mesenchymal stromal cells transfected with GFP gene into thrombosed femoral vein was studied by fluorescent microscopy. Vascular thrombosis caused by ligation of the great vein with subsequent injection of thrombin solution was accompanied by blockade of regional lymph flow. The cells injected into thrombosed vein directly participate in the formation of new lymphatic vessels in the paravasal tissue surrounding the vein, its tissue region, and around regional lymph nodes. This is seen from bright specific fluorescence of individual cells in the walls of lymphatic vessels and all vascular layers and valves in UV light.
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PMID:Possibility of Using Mesenchymal Stromal Cells to Restore Lymph Flow in Experimental Phlebothrombosis. 2689 41

In the male Wag rats aged 6 months with the body mass of 180-200 g the luminescent microscopy was used to examine the possibility of lymphatic vessel formation after injection into thrombosed vein of the thigh of autologous multipotent stromal cells of bone marrow origin (AMSCBMO) transfected with green fluorescent protein gene. Animals were sacrificed 4 days and 1, 2, 3, 4 and 5 weeks after the injection of AMSCBMO. The control group consisted of intact rats, animals with venous thrombosis receiving no injection of AMSCBMO and those injected with AMSCBMO but without the prior modelling of venous thrombosis. In each experimental and control groups at each time point 11-12 animals were used (total number equal to 226). After the main vein ligation with the subsequent injection of thrombin solution, in addition to the thrombosis of the blood vessels, morphological signs of thrombosis of the lymphatic bed and lymphostasis were present: the dilation of lymphatic vessel lumen, thinning of their layers, intense staining of their luminal heterogeneous content. AMSCBMO, injected into thrombosed vein, were found to directly participate in lymphangiogenesis in the connective tissue around vein, its tissue region and in the area of regional lymph nodes. This is indicated by bright specific luminescence of both individual cells in the wall of the lymphatic vessels, and all their tunics together with the valves, when exposed to UV light.
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PMID:[MORPHOLOGICAL CHANGES AFTER THE USE OF MULTIPOTENT STROMAL CELLS OF BONE MARROW ORIGIN TO RESTORE THE LYMPH FLOW IN THE REGION OF THROMBOSED VEIN]. 2698 18

Von Willebrand factor (VWF) serves as a nidus for platelet aggregation and thrombosis. We hypothesize that VWF fibers contribute to the development of venous thromboembolism (VTE) and to metastasis formation. Here, we show that vascular and lymphatic endothelial cells (ECs) express VWF in vitro and release VWF fibers after activation by tumor cell supernatants. In contrast, an ex vivo analysis of primary mouse tumors revealed the presence of VWF fibers in the blood microvasculature but not in lymphatic vessels. Unlike the anticoagulant Fondaparinux, an inhibitor of thrombin generation, the low-molecular-weight heparin (LMWH) Tinzaparin inhibited VWF fiber formation and vessel occlusion in tumor vessels by blocking thrombin-induced EC activation and vascular endothelial growth factor-A (VEGF-A)-mediated VWF release. Intradermal tumor cell inoculation in VWF- and ADAMTS13-deficient mice did not alter lymph node metastases compared with wild type animals. Interestingly, multiple tumor-free distal organs exhibited hallmarks of malignancy-related VTE, including luminal VWF fibers, platelet-rich thrombi and vessel occlusions. Furthermore, ADAMTS13 deficiency, characterized by prolonged intraluminal VWF network lifetimes, resulted in a severely increased number of metastatic foci in an experimental model of hematogenous lung seeding. Treatment with Tinzaparin inhibited tumor-induced release of VWF multimers, impeded platelet aggregation and decreased lung metastasis. Thus, our data strongly suggest a critical role of luminal VWF fibers in determining the occurrence of thrombosis and cancer metastasis. Moreover, the findings highlight LMWHs as therapeutic strategy to treat thrombotic complications while executing anti-metastatic activities.
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PMID:Heparins that block VEGF-A-mediated von Willebrand factor fiber generation are potent inhibitors of hematogenous but not lymphatic metastasis. 2760 96

Hemostasis associated with tissue injury is followed by wound healing, a complex process by which damaged cellular material is removed and tissue repaired. Angiogenic responses are a central aspect of wound healing, including the growth of new lymphatic vessels by which immune cells, protein, and fluid are transported out of the wound area. The concept that hemostatic responses might be linked to wound healing responses is an old one, but demonstrating such a link in vivo and defining specific molecular mechanisms by which the 2 processes are connected has been difficult. In the present study, we demonstrate that the lymphangiogenic factors vascular endothelial growth factor C (VEGFC) and VEGFD are cleaved by thrombin and plasmin, serine proteases generated during hemostasis and wound healing. Using a new tail-wounding assay to test the relationship between clot formation and lymphangiogenesis in mice, we find that platelets accelerate lymphatic growth after injury in vivo. Genetic studies reveal that platelet enhancement of lymphatic growth after wounding is dependent on the release of VEGFC, but not VEGFD, a finding consistent with high expression of VEGFC in both platelets and avian thrombocytes. Analysis of lymphangiogenesis after full-thickness skin excision, a wound model that is not associated with significant clot formation, also revealed an essential role for VEGFC, but not VEGFD. These studies define a concrete molecular and cellular link between hemostasis and lymphangiogenesis during wound healing and reveal that VEGFC, the dominant lymphangiogenic factor during embryonic development, continues to play a dominant role in lymphatic growth in mature animals.
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PMID:Hemostasis stimulates lymphangiogenesis through release and activation of VEGFC. 3156 36