{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:17:08Z","timestamp":1791346628836,"version":"4.3.1"},"reference-count":27,"publisher":"American Society of Hematology","issue":"7","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The vessel wall endothelium undoubtedly plays a role in the vascular pathobiology of sickle cell disease. This pilot study tested the feasibility of using an inhibitor of nuclear factor (NF)\u2013\u03baB, a transcription factor, to modify the endothelial activation state of patients with this vascular disease. For a total of 7 separate drug exposure tests, 3 subjects with sickle cell disease took sulfasalazine (given orally at 1 g every 8 hours), and the activation state of their circulating endothelial cells (CECs) was assessed using immunofluorescence microscopy. Companion studies were also performed using sulfasalazine in sickle transgenic mice to verify its effect simultaneously on both CECs and vessel wall endothelium. Both CECs and tissue vessel wall endothelium in sickle mice have an activated phenotype. In these mice sulfasalazine significantly reduced CEC expression of vascular cell adhesion molecule (VCAM), intracellular adhesion molecule (ICAM), and E-selectin, and it correspondingly reduced expression of these molecules in some tissue vessels. In humans with sickle cell disease, sulfasalazine significantly reduced CEC expression of VCAM, ICAM, and E-selectin, but it did not reduce expression of tissue factor. Addition of a second transcription factor inhibitor, salsalate, did not change this result. This pilot study suggests that endothelial cell activation state can be modified and down-regulated in vivo by sulfasalazine.<\/jats:p>","DOI":"10.1182\/blood.v97.7.1937","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T12:46:47Z","timestamp":1027774007000},"page":"1937-1941","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":122,"title":["Modulation of endothelial cell activation in sickle cell disease: a pilot study"],"prefix":"10.1182","volume":"97","author":[{"given":"Alex A.","family":"Solovey","sequence":"first","affiliation":[{"name":"From the Department of Medicine, University of Minnesota Medical School, Minneapolis."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna N.","family":"Solovey","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, University of Minnesota Medical School, Minneapolis."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanne","family":"Harkness","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, University of Minnesota Medical School, Minneapolis."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert P.","family":"Hebbel","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, University of Minnesota Medical School, Minneapolis."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2020021217215700000_B1","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/S0022-2143(97)90176-1","article-title":"The endothelial biology of sickle cell disease.","volume":"129","author":"Hebbel","year":"1997","journal-title":"J Lab Clin Med."},{"key":"2020021217215700000_B2","first-page":"311","article-title":"Pathogenesis of vasoocclusion.","volume-title":"Sickle Disease: Basic Principles and Clinical Practice.","author":"Embury","year":"1994"},{"key":"2020021217215700000_B3","doi-asserted-by":"crossref","first-page":"2561","DOI":"10.1172\/JCI119442","article-title":"Adhesive interactions of sickle erythrocytes with endothelium.","volume":"99","author":"Hebbel","year":"1997","journal-title":"J Clin Invest."},{"key":"2020021217215700000_B4","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1056\/NEJM199711273372203","article-title":"Circulating activated endothelial cells in sickle cell anemia.","volume":"337","author":"Solovey","year":"1997","journal-title":"N Engl J Med."},{"key":"2020021217215700000_B5","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1172\/JCI1932","article-title":"Tissue factor expression by endothelial cells in sickle cell anemia.","volume":"101","author":"Solovey","year":"1998","journal-title":"J Clin Invest."},{"key":"2020021217215700000_B6","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1097\/00007890-199010000-00001","article-title":"The role of endothelial cells in inflammation.","volume":"50","author":"Pober","year":"1990","journal-title":"Transplantation."},{"key":"2020021217215700000_B7","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1182\/blood.V96.1.314","article-title":"Reperfusion injury pathophysiology in sickle transgenic mice.","volume":"96","author":"Osarogiagbon","year":"2000","journal-title":"Blood."},{"key":"2020021217215700000_B8","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1172\/JCI9225","article-title":"Hypoxia\/reoxygenation causes inflammatory response in transgenic sickle mice but not in normal mice.","volume":"106","author":"Kaul","year":"2000","journal-title":"J Clin Invest."},{"key":"2020021217215700000_B9","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1172\/JCI992","article-title":"Sulfasalazine: a potent and specific inhibitor of nuclear factor kappa B.","volume":"101","author":"Wahl","year":"1998","journal-title":"J Clin Invest."},{"key":"2020021217215700000_B10","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1146\/annurev.immunol.16.1.225","article-title":"NF-kB and rel proteins: evolutionarily conserved mediators of immune responses.","volume":"16","author":"Ghosh","year":"1998","journal-title":"Annu Rev Immunol."},{"key":"2020021217215700000_B11","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1056\/NEJM199704103361506","article-title":"Nuclear factor-\u03baB: a pivotal transcription factor in chronic inflammatory diseases.","volume":"336","author":"Barnes","year":"1997","journal-title":"New Eng J Med."},{"key":"2020021217215700000_B12","doi-asserted-by":"crossref","first-page":"12155","DOI":"10.1073\/pnas.89.24.12155","article-title":"High expression of human betaS- and alpha-globins in transgenic mice: erythrocyte abnormalities, organ damage, and the effect of hypoxia.","volume":"89","author":"Fabry","year":"1992","journal-title":"Proc Natl Acad Sci U S A."},{"key":"2020021217215700000_B13","first-page":"3527","article-title":"Endothelial cells in physiology and in the pathophysiology of vascular disorders.","volume":"91","author":"Cines","year":"1998","journal-title":"Blood."},{"key":"2020021217215700000_B14","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1096\/fasebj.9.10.7615158","article-title":"Regulation of the tissue factor gene.","volume":"9","author":"Mackman","year":"1995","journal-title":"FASEB J."},{"key":"2020021217215700000_B15","doi-asserted-by":"crossref","first-page":"3849","DOI":"10.1074\/jbc.270.8.3849","article-title":"Regulation of the tissue factor promoter in endothelial cells.","volume":"270","author":"Moll","year":"1995","journal-title":"J Biol Chem."},{"key":"2020021217215700000_B16","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1126\/science.270.5244.2017","article-title":"The effect of sodium salicylate and aspirin on NF-\u03baB.","volume":"270","author":"Franz","year":"1995","journal-title":"Science."},{"key":"2020021217215700000_B17","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1126\/science.270.5234.286","article-title":"Immunosuppression by glucocorticoids: inhibition of NF-kB activity through induction of IkB synthesis.","volume":"270","author":"Auphan","year":"1995","journal-title":"Science."},{"key":"2020021217215700000_B18","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1126\/science.8052854","article-title":"Inhibition of NK-kB by sodium salicylate and aspirin.","volume":"265","author":"Kopp","year":"1994","journal-title":"Science."},{"key":"2020021217215700000_B19","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1006\/bbrc.1996.1483","article-title":"An in vivo cytokine and endotoxin-independent pathway for induction of nitric oxide synthase II mRNA, enzyme, and nitrate\/nitrite in alveolar macrophages.","volume":"227","author":"Greenberg","year":"1996","journal-title":"Biochem Biophys Res Commun."},{"key":"2020021217215700000_B20","doi-asserted-by":"crossref","first-page":"2842","DOI":"10.1172\/JCI119477","article-title":"Glucocorticoid-mediated repression of cytokine gene transcription in human arteritis-SCID chimeras.","volume":"99","author":"Brack","year":"1997","journal-title":"J Clin Invest."},{"key":"2020021217215700000_B21","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1097\/00001756-199802160-00024","article-title":"Central nervous system DNA fragmentation induced by the inhibition of nuclear factor kappa B.","volume":"9","author":"Taglialatela","year":"1998","journal-title":"Neuroreport."},{"key":"2020021217215700000_B22","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1038\/nm0897-894","article-title":"In vivo transfection of cis element \u201cdecoy\u201d against nuclear factor-kB binding site prevents myocardial infarction.","volume":"3","author":"Morishita","year":"1997","journal-title":"Nat Med."},{"key":"2020021217215700000_B23","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1056\/NEJM199403173301101","article-title":"High-dose intravenous methylprednisolone therapy for pain in children and adolescents with sickle cell disease.","volume":"330","author":"Griffin","year":"1994","journal-title":"New Engl J Med."},{"key":"2020021217215700000_B24","doi-asserted-by":"crossref","first-page":"3082","DOI":"10.1182\/blood.V92.9.3082","article-title":"Beneficial effect of intravenous dexamethasone in children with mild to moderately severe acute chest syndrome.","volume":"92","author":"Bernini","year":"1998","journal-title":"Blood."},{"key":"2020021217215700000_B25","first-page":"676a","article-title":"Therapeutic modulation of vascular endothelial cell activation state as therapy for sickle cell disease: NF-\u03baB inhibition as a strategy [abstract].","volume":"94","author":"Solovey","year":"1999","journal-title":"Blood."},{"key":"2020021217215700000_B26","doi-asserted-by":"crossref","first-page":"2451","DOI":"10.1182\/blood.V96.7.2451","article-title":"Activated monocytes in sickle cell disease: potential role in the activation of vascular endothelium and vaso-occlusion.","volume":"96","author":"Belcher","year":"2000","journal-title":"Blood."},{"key":"2020021217215700000_B27","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1056\/NEJM199901143400207","article-title":"Atherosclerosis: an inflammatory disease.","volume":"340","author":"Epstein","year":"1999","journal-title":"N Engl J Med."}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/97\/7\/1937\/1672247\/h8070101937.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/97\/7\/1937\/1672247\/h8070101937.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,2,12]],"date-time":"2020-02-12T23:12:48Z","timestamp":1581549168000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/97\/7\/1937\/53410\/Modulation-of-endothelial-cell-activation-in"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,4,1]]},"references-count":27,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2001,4,1]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.v97.7.1937","relation":{},"ISSN":["1528-0020","0006-4971"],"issn-type":[{"value":"1528-0020","type":"electronic"},{"value":"0006-4971","type":"print"}],"subject":[],"published":{"date-parts":[[2001,4,1]]}}}