{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T14:42:21Z","timestamp":1772894541112,"version":"3.50.1"},"reference-count":28,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Physiological Genomics"],"published-print":{"date-parts":[[2005,5,11]]},"abstract":"<jats:p>Clinical variability in sickle cell disease (SCD) suggests a role for extra-erythrocytic factors in the pathogenesis of vasoocclusion. We hypothesized that endothelial cell (EC) dysfunction, one possible modifier of disease variability, results from induction of phenotypic changes by circulating factors. Accordingly, we analyzed gene expression in cultured human pulmonary artery ECs (HPAEC) exposed to plasma from 1) sickle acute chest syndrome (ACS) patients, 2) SCD patients at steady state, 3) normal volunteers, and 4) serum-free media, using whole genome microarrays (U133A-B GeneChip, Affymetrix). Data were analyzed by Bayesian analysis of differential gene expression (BADGE). Differential expression was defined by the probability of &gt;1.5 fold change in signal intensity greater than 0.999 and a predicted score of 70\u2013100, measured by cross-validation. Compared with normal plasma, plasma from SCD patients (steady state) resulted in differential expression of 50 genes in HPAEC. Of these genes, molecules involved in cholesterol biosynthesis and lipid transport, the cellular stress response, and extracellular matrix proteins were most prominent. Another 58 genes were differentially expressed in HPAEC exposed to plasma from ACS patients. The pattern of altered gene expression suggests that plasma from SCD patients induces an EC phenotype which is anti-apoptotic and favors cholesterol biosynthesis. An altered EC phenotype elicited by SCD plasma may contribute to the pathogenesis of sickle vasoocclusion.<\/jats:p>","DOI":"10.1152\/physiolgenomics.00246.2004","type":"journal-article","created":{"date-parts":[[2005,3,2]],"date-time":"2005-03-02T03:49:03Z","timestamp":1109735343000},"page":"293-298","source":"Crossref","is-referenced-by-count":16,"title":["Differential gene expression in pulmonary artery endothelial cells exposed to sickle cell plasma"],"prefix":"10.1152","volume":"21","author":[{"given":"Elizabeth S.","family":"Klings","sequence":"first","affiliation":[{"name":"The Pulmonary Center, Boston University School of Public Health, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Surinder","family":"Safaya","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, Boston University School of Public Health, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adeboye H.","family":"Adewoye","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, Boston University School of Public Health, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Odhiambo","sequence":"additional","affiliation":[{"name":"The Pulmonary Center, Boston University School of Public Health, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Garrett","family":"Frampton","sequence":"additional","affiliation":[{"name":"Department of Genetics\/Genomics, Boston University School of Medicine, Boston University School of Public Health, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Lenburg","sequence":"additional","affiliation":[{"name":"Department of Genetics\/Genomics, Boston University School of Medicine, Boston University School of Public Health, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norman","family":"Gerry","sequence":"additional","affiliation":[{"name":"Department of Genetics\/Genomics, Boston University School of Medicine, Boston University School of Public Health, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Sebastiani","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin H.","family":"Steinberg","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, Boston University School of Public Health, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harrison W.","family":"Farber","sequence":"additional","affiliation":[{"name":"The Pulmonary Center, Boston University School of Public Health, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.45.10.902"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2143(99)90191-9"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-03-0948"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.4.2404-2412.2005"},{"key":"R5","unstructured":"Embury SH, Hebbel RP, Mohandas N, and Steinberg MH.Pathogenesis of Vasoocclusion.New York: Lippincott-Raven, 1994."},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa035477"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1999.277.4.H1579"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.156.1.9611085"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2004.01.031"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1667\/0033-7587(2002)157[0650:HHIIIT]2.0.CO;2"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1995.269.5.C1105"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-4608(03)00300-5"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.24.8567"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1215\/S1152851703000632"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2004.09.033"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118102"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1177\/154407370301700124"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-03-0693"},{"key":"R19","doi-asserted-by":"crossref","unstructured":"Shiu YT, Udden MM, and McIntire LV.Perfusion with sickle erythrocytes up-regulates ICAM-1 and VCAM-1 gene expression in cultured human endothelial cells.Blood95: 3232\u20133241, 2000.","DOI":"10.1182\/blood.V95.10.3232.010k16_3232_3241"},{"key":"R20","unstructured":"Shores J, Peterson J, VanderJagt D, and Glew RH.Reduced cholesterol levels in African-American adults with sickle cell disease.J Natl Med Assoc95: 813\u2013817, 2003."},{"key":"R21","unstructured":"Solovey A, Gui L, Ramakrishnan S, Steinberg MH, and Hebbel RP.Sickle cell anemia as a possible state of enhanced anti-apoptotic tone: survival effect of vascular endothelial growth factor on circulating and unanchored endothelial cells.Blood93: 3824\u20133830, 1999."},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.10210"},{"key":"R23","doi-asserted-by":"crossref","unstructured":"Sultana C, Shen Y, Rattan V, Johnson C, and Kalra VK.Interaction of sickle erythrocytes with endothelial cells in the presence of endothelial cell conditioned medium induces oxidant stress leading to transendothelial migration of monocytes.Blood92: 3924\u20133935, 1998.","DOI":"10.1182\/blood.V92.10.3924.422k07_3924_3935"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700142"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0401715101"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1097\/00019606-200403000-00008"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200006223422502"},{"key":"R28","unstructured":"Vichinsky EP, Styles LA, Colangelo LH, Wright EC, Castro O, and Nickerson B.Acute chest syndrome in sickle cell disease: clinical presentation and course. Cooperative Study of Sickle Cell Disease.Blood89: 1787\u20131792, 1997."}],"container-title":["Physiological Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/physiolgenomics.00246.2004","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,4,6]],"date-time":"2020-04-06T02:21:04Z","timestamp":1586139664000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/physiolgenomics.00246.2004"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,5,11]]},"references-count":28,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2005,5,11]]}},"alternative-id":["10.1152\/physiolgenomics.00246.2004"],"URL":"https:\/\/doi.org\/10.1152\/physiolgenomics.00246.2004","relation":{},"ISSN":["1094-8341","1531-2267"],"issn-type":[{"value":"1094-8341","type":"print"},{"value":"1531-2267","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,5,11]]}}}