Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039483 (giant cell arteritis)
 3,204 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Markers of endothelial cell activation were measured in 28 patients presenting with various forms of limited or focal type cutaneous vasculitis. Plasma levels of tissue plasminogen activator antigen (t-PA:Ag), plasminogen activator inhibitor type 1 antigen (PAI-1:Ag) and PAI-1 activity, fibrin plate, von Willebrand factor antigen (vWF:Ag), tissue factor (TF) and soluble thrombomodulin (sTM) were measured. In comparison with the control group (n = 20) there was a significant increase in t-PA:Ag, vWF:Ag and TF (P < 0.05, Mann-Whitney U-test) in the cutaneous vasculitis group. This study confirms that measurable degrees of endothelial activation occur in cutaneous vasculitis. Cutaneous vasculitis includes a diverse group of clinical conditions, which are associated with inflammatory changes in cutaneous blood vessels with local fibrin deposition. The aetiology and pathogenesis of the majority of these entities remain unknown. Causative mediators are thought to include immune complexes, anti-endothelial cell antibodies, cytotoxic lymphocytes and viruses. Histologically, immune complexes and complement are frequently detected on the vessel wall, and serologically anti-endothelial antibodies are often detected in patients with vasculitis and in systemic lupus erythematosus (SLE) which correlate with the severity of cutaneous vasculitis, arthritis and nephritis. Lymphocyte-mediated toxicity to endothelial cells has been reported in a small number of patients with giant cell arteritis and Takayasu's arteritis. The vascular endothelium plays a central part in the control of haemostasis. Under physiological conditions endothelial cells present an anticoagulant surface to blood constituents, partially due to surface expression of heparan sulphate and thrombomodulin (TM). Heparan sulphate binds antithrombin III (ATIII), thereby accelerating inactivation of intrinsic coagulation enzymes. Thrombomodulin is an endothelial cell surface glycoprotein which promotes anticoagulation by forming a complex with thrombin which then activates protein C. Activated protein C together with a cofactor, protein S, inactivates FVa and FVIIIa. von Willebrand factor (vWF) is synthesized by endothelial cells, stored in Weibel-Palade bodies and released into the circulation upon endothelial stimulation. vWF mediates the binding of platelets to the subendothelium and is the carrier molecule for FVIIIC. The endothelium controls fibrinolysis by producing t-PA and its inhibitor PAI-1. Inflammatory cytokines such as interleukin-1 (IL-1) and tumour necrosis factor (TNF) activate endothelial cells, causing a shift from an antithrombotic to prothrombotic state, including expression of tissue factor, increased synthesis of PAI-1 and decreased expression of TM. Fibrin deposition and intravascular thrombosis are seen in cutaneous vasculitis syndromes, suggesting local endothelial cell activation. The aim of this pilot study was to assess whether perturbation of the endothelium in cutaneous vasculitis could be detected in the patients' plasma samples. If so, further studies to assess any correlation in levels of these markers with disease activity might prove useful in the future.
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PMID:Endothelial cell activation in cutaneous vasculitis. 868 65

Ischemia is a leading causes of morbidity in giant cell arteritis (GCA). We studied circulating platelets and leukocytes in patients with GCA and with polymyalgia rheumatica. Normal healthy donors (>60 a) served as controls. Patients had a significantly greater fraction of platelets expressing P-selectin, of platelet-Nph and platelet-Mo aggregates, and of Nph and Mo expressing tissue factor. These differences were correlated with the percentage of platelets expressing P-selectin and were not influenced by clinical features or by systemic inflammation. Activated circulating leukocytes and platelets could contribute to indolent vessel inflammation and possibly to thromboembolic events in patients with systemic large vessel vasculitis.
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PMID:Leukocyte and platelet activation in patients with giant cell arteritis and polymyalgia rheumatica: a clue to thromboembolic risks? 1981 9

Epidemiologic studies have shown that the neutrophil count correlates with the risk of myocardial infarction and stroke and identify patients more susceptible to reinfarction and in-hospital death. In particular, neutrophils action was initially associated to blood rheological changes, or to the effect of neutrophil-derived eicosanoids or proteases. Animal models indicate that platelet-leukocyte P-selectin dependent cross-talk contributes to fibrin deposition during in vivo thrombus formation. In fact, platelet P-selectin, through its leukocyte counter-receptor PSGL-1, determines the activation of leukocyte beta2 integrins, the binding of fibrinogen and the expression of tissue factor on leukocyte surface. Monocytes stimulated in vitro with LPS, PMA and P-selectin synthesize and express tissue factor, fMLP, P-selectin, TNFalpha and C5a are effective stimuli that trigger the synthesis and expression of biologically active tissue factor in neutrophils. The experimental evidence well agrees with clinical observations: patients with acute coronary syndromes, acute respiratory distress syndrome, antiphospholipid syndromes, giant cell arteritis and myeloproliferative syndromes have increased the expression of tissue factor on leukocyte surface. Moreover circulating neutrophils express mRNA codifying for full-length and/or alternatively spliced tissue factor, suggesting a new important link between thrombosis and inflammation. All together, clinical and experimental evidence suggest that the leukocyte thrombogenic profile is a relevant player in patients with a high risk of thromboembolic events and possibly represents a suitable target for molecular intervention.
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PMID:Clinical and experimental evidences on the prothrombotic properties of neutrophils. 2022 83