Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149871 (deep vein thrombosis)
 12,364 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

P-selectin glycoprotein ligand (PSGL-1) shares common features with platelet glycoprotein Ibalpha. A recently described polymorphism in this receptor that results in a variable number of tandem repeats (VNTR) sequence present either 16, 15 or 14 times (alleles A, B or C) could, similar to GPIbalpha, be functionally relevant. The allelic frequency of this polymorphism was investigated in 469 individuals from the south of Spain, and was similar to that previously described in other Caucasian populations: 85% A, 14% B and 1% C alleles. We identified two new polymorphisms genetically linked to the C isoform, resulting in the Ser273Phe and Met274Val changes. To assess the functional consequence of the polymorphisms in the receptor, we performed flow cytometric analysis of P-selectin dependent neutrophil-platelet interaction. Neutrophils carrying the shortest C allele and the amino acid variations in residues 273 and 274 exhibited a significantly lower capacity to bind activated platelets than A/B and A/A samples (mean fluorescence intensity of CD42b+ neutrophils 262 versus 303 and 319 respectively, P < 0.05). The distribution of the VNTR was analysed in three case-control studies including 104 cerebrovascular (CVD), 101 coronary heart disease (CHD) and 150 deep venous thrombosis (DVT) patients. The results showed that smaller (B and C) alleles seem to be associated with a lower risk of developing CVD (P = 0.008) but not to be related to CHD or DVT. In conclusion, polymorphisms of the PSGL-1 receptor may influence the neutrophil-platelet binding, and represent a risk factor for CVD.
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PMID:Polymorphisms of P-selectin glycoprotein ligand-1 are associated with neutrophil-platelet adhesion and with ischaemic cerebrovascular disease. 1184 35

Platelets contribute to blood coagulation at sites of vascular injury and to the recruitment of leukocytes at sites of inflammation. Under pathological conditions, platelets are involved in numerous diseases and clinical complications, such as deep venous thrombosis, embolism and atherosclerosis. But so far, little is known about the mechanisms of inflammation in large veins and the role of platelets in inflamed large veins. For this purpose, we investigated primary and secondary interactions between platelets, leukocytes and endothelial cells in the femoral vein in vivo with special regard to the role of CD62P (P-selectin) and CD162 (PSGL-1). Mice were challenged with lipopolysaccharide (LPS)/D-galactosamine (D-gal) and either CD162 or CD62P was blocked by intravenous administration of a corresponding antibody at the time point of LPS/D-gal injection. Four hours after LPS/gal injection, intravital fluorescence microscopy of the femoral vein was performed and primary and secondary platelet-leukocyte-endothelial cell-interactions were visualized after in vivo platelet and leukocyte staining with rhodamine 6G. Analysis of intravital fluorescence microscopy revealed that LPS/D-gal caused a strong inflammatory reaction of the venous endothelium with significant induction of platelet and leukocyte tethering, rolling and adhesion. Secondary interactions of platelets to adherent or rolling platelets or leukocytes were also increased after LPS/D-gal-injection. Immunoneutralization of either CD162 or CD62P significantly decreased platelet primary and secondary capture as well as leukocyte rolling and adhesion. CD162 and CD62P play a central role in mediating inflammatory primary and secondary interactions of platelets and leukocytes to the endothelium in inflamed large veins in vivo. Thus, blocking CD162 or CD62P might be an attractive tool for preventing platelet and leukocyte-driven venous diseases.
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PMID:Capture of platelets to the endothelium of the femoral vein is mediated by CD62P and CD162. 1985 90