{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T20:50:29Z","timestamp":1791060629532,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2010,1,7]],"date-time":"2010-01-07T00:00:00Z","timestamp":1262822400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2010,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the expression of protease\u2010activated receptors (PARs), their potential regulation by anticardiolipin antibodies (aCL), and their association with the expression of other molecules relevant to thrombosis in monocytes obtained from 62 patients with primary antiphospholipid syndrome (APS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Monocytes were isolated from peripheral blood mononuclear cells by magnetic depletion of nonmonocytes. Expression of tissue factor (TF) and PARs 1\u20134 genes was measured by quantitative real\u2010time reverse transcription\u2013polymerase chain reaction. Cell surface TF and PARs 1\u20134 expression was analyzed by flow cytometry. For in vitro studies, purified normal monocytes were incubated with purified APS patient IgG, normal human serum IgG, or lipopolysaccharide, in the presence or absence of specific monoclonal antibodies anti\u2013PAR\u20101 (ATAP2) or anti\u2013PAR\u20102 (SAM11) to test the effect of blocking the active site of PAR\u20101 or PAR\u20102.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Analysis of both mRNA and protein for the 4 PARs revealed significantly increased expression of PAR\u20102 as compared with the control groups. PAR\u20101 was significantly overexpressed in APS patients with thrombosis and in the control patients with thrombosis but without APS. PAR\u20103 expression was not significantly altered. PAR\u20104 expression was absent in all groups analyzed. In addition, we demonstrated a correlation between the levels of PAR\u20102 and the titers of IgG aCL, as well as parallel behavior of TF and PAR\u20102 expression. In vitro, IgG from APS patients significantly increased monocyte expression of PAR\u20101 and PAR\u20102. Inhibition studies suggested that there was direct cross\u2010talk between TF and PAR\u20102, such that inhibition of PAR\u20102 prevented the aCL\u2010induced expression of TF.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results provide the first demonstration of increased expression of PARs in monocytes from patients with APS. Thus, PAR antagonists might have therapeutic potential as antithrombotic agents in APS.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.27299","type":"journal-article","created":{"date-parts":[[2010,1,7]],"date-time":"2010-01-07T17:54:50Z","timestamp":1262886890000},"page":"869-877","source":"Crossref","is-referenced-by-count":54,"title":["Differential expression of protease\u2010activated receptors in monocytes from patients with primary antiphospholipid syndrome"],"prefix":"10.1002","volume":"62","author":[{"given":"Chary","family":"L\u00f3pez\u2010Pedrera","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria \u00c1ngeles","family":"Aguirre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Buend\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"Barbarroja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Ruiz\u2010Lim\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Collantes\u2010Estevez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Velasco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munther","family":"Khamashta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Jos\u00e9","family":"Cuadrado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,2,25]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2006.01753.x"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2007.09.001"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1177\/0961203308090025"},{"key":"e_1_2_7_5_2","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1532\/IJH97.03165","article-title":"Progress in the understanding of protease\u2010activated receptors","volume":"70","author":"Gabazza EC","year":"2004","journal-title":"Int J Hematol"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.20.11023"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/35025229"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.92.9.428"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.567297"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780400509"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1614977"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1614881"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200111)44:11<2467::AID-ART426>3.0.CO;2-U"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21009"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21549"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-01-070631"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.141126698"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000171155.05809.bf"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2005.01377.x"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-08-2497"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1649901"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-01-070631"},{"key":"e_1_2_7_23_2","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1161\/01.ATV.0000151624.45775.13","article-title":"Tissue factor\u2010factor VIIa signalling","volume":"25","author":"Rhao LV","year":"2005","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2005.06.005"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2006.02193.x"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1037"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.10.5255"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M401376200"},{"key":"e_1_2_7_29_2","first-page":"3453","article-title":"Neutrophil activation by the tissue factor\/factor VIIa\/PAR\u20102 axis mediates fetal death in a mouse model of antiphospholipid syndrome","volume":"118","author":"Redecha P","year":"2008","journal-title":"J Clin Invest"}],"container-title":["Arthritis &amp; 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