title: A prospective, observational study of soluble FLT-1 and vascular endothelial growth factor in sepsis.
abstract: Prior murine and human studies suggest that vascular endothelial growth factor (VEGF) contributes to endothelial cell activation and severity of illness in sepsis. Furthermore, circulating levels of soluble VEGF receptor 1 (sFLT) levels were found to increase as part of the early response to sepsis in mice. The objective of the study was to evaluate the blood levels of free VEGF-A and sFLT in patients presenting to the emergency department (ED) with suspected infection and to assess the relationship of these levels with severity of illness and inflammation. It was a prospective, observational study initiated in the ED of an urban, tertiary care, university hospital. Inclusion criteria were (1) ED patients aged 18 years or older and (2) clinical suspicion of infection. Eighty-three patients were enrolled in the study. The major findings were that (1) the mean VEGF and sFLT levels were increasingly higher across the following groups: noninfected control patients, infected patients without shock, and septic shock patients; (2) initial and 24-h VEGF levels had a significant correlation with the presence of septic shock at 24 h; (3) initial and 24-h sFLT levels correlated with Acute Physiology Age Chronic Health Evaluation II and Sepsis-related Organ/Failure Assessment scores initially and at 24 h; and (4) VEGF and sFLT levels correlated with inflammatory cascade activation. This is the first report of sFLT as a potential new marker of severity in patients with sepsis. Vascular endothelial cell growth factor and its signaling axis are important in the endothelial cell response to sepsis, and further elucidation of these mechanisms may lead to advances in future diagnostic and therapeutic opportunities.
authors.affiliation: Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, Masachusetts 02215, USA. nshapiro@bidmc.harvard.edu
authors.forename: Nathan I
authors.initials: NI
authors.lastname: Shapiro
authors.forename: Kiichiro
authors.initials: K
authors.lastname: Yano
authors.forename: Hitomi
authors.initials: H
authors.lastname: Okada
authors.forename: Christopher
authors.initials: C
authors.lastname: Fischer
authors.forename: Michael
authors.initials: M
authors.lastname: Howell
authors.forename: Katherine C
authors.initials: KC
authors.lastname: Spokes
authors.forename: Long
authors.initials: L
authors.lastname: Ngo
authors.forename: Derek C
authors.initials: DC
authors.lastname: Angus
authors.forename: William C
authors.initials: WC
authors.lastname: Aird
mesh_terms: D018806:APACHE; D000368:Aged; D004636:Emergency Service, Hospital; D006801:Humans; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008875:Middle Aged; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood* / Q000473:pathology; D012995:Solubility; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1