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To determine the importance of vascular endothelial growth factor A (VEGF-A) in this syndrome, we compared plasma levels of VEGF-A and the soluble forms of its receptors in patients with DHF to patients with dengue fever (DF), a milder form of dengue virus infection without plasma leakage. We observed a rise in the plasma levels of free, but not total VEGF-A in DHF patients at the time of plasma leakage. This was associated with a decline in the soluble form of VEGF receptor 2 (VEGFR2) and VEGF-soluble VEGFR2 complexes, but not the soluble form of VEGFR1. The severity of plasma leakage in patients inversely correlated with plasma levels of soluble VEGFR2. In vitro, dengue virus suppressed soluble VEGFR2 production by endothelial cells but up-regulated surface VEGFR2 expression and promoted response to VEGF stimulation. In vivo, plasma viral load correlated with the degree of decline in plasma soluble VEGFR2. These results suggest that VEGF regulates vascular permeability and its activity is controlled by binding to soluble VEGFR2. Dengue virus-induced changes in surface and soluble VEGFR2 expression may be an important mechanism of plasma leakage in DHF.<\/jats:p>","DOI":"10.1128\/jvi.01642-06","type":"journal-article","created":{"date-parts":[[2006,12,7]],"date-time":"2006-12-07T14:57:14Z","timestamp":1165503434000},"page":"1592-1600","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":125,"title":["Virus-Induced Decline in Soluble Vascular Endothelial Growth Receptor 2 Is Associated with Plasma Leakage in Dengue Hemorrhagic Fever"],"prefix":"10.1128","volume":"81","author":[{"given":"Anon","family":"Srikiatkhachorn","sequence":"first","affiliation":[{"name":"Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, Massachusetts 01655"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanpis","family":"Ajariyakhajorn","sequence":"additional","affiliation":[{"name":"Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand 10400"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy P.","family":"Endy","sequence":"additional","affiliation":[{"name":"Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand 10400"},{"name":"Infectious Disease Division, Department of Medicine, State University of New York, Upstate Medical University, Syracuse, New York 13210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siripen","family":"Kalayanarooj","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Queen Sirikit National Institute of Child Health, Bangkok, Thailand 10400"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel H.","family":"Libraty","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, Massachusetts 01655"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharone","family":"Green","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, Massachusetts 01655"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis A.","family":"Ennis","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, Massachusetts 01655"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan L.","family":"Rothman","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, Massachusetts 01655"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s003830200012"},{"key":"e_1_3_2_3_2","first-page":"2898","volume":"60","year":"2000","unstructured":"Adams, J., P. 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