title: Preeclampsia is associated with lower production of vascular endothelial growth factor by peripheral blood mononuclear cells.
abstract: BACKGROUND
  Recent studies show that vascular endothelial growth factor (VEGF) downregulation is implicated in preeclampsia (PE) pathophysiology. This study assessed the relationship between PE and VEGF levels produced by peripheral blood mononuclear cells (PBMCs) and their serum levels.
  
  
  METHODS
  A cross-sectional design was performed in 36 patients who had hypertensive disorders during pregnancy. We also used a longitudinal design with 12 pregnant women with risk factors for PE development and/or abnormal uterine arteries by Doppler study. VEGF and soluble fms-like tyrosine kinase-1 (sFlt-1) levels were measured for all patients in both designs.
  
  
  RESULTS
  sFlt-1 serum was higher in preeclamptic patients (n = 26), whereas VEGF produced by stimulated PBMCs was lower than in healthy pregnant women and VEGF levels produced by stimulated PBMCs were even lower (p <0.003) in severe PE (n = 16). The receiver-operating characteristic curve analysis allowed establishing a cut-off value to identify patients with PE. VEGF production by PBMCs was 339.87 pg/mL. In addition, a robust linear regression model was performed to adjust the variance in VEGF levels. The patients' age decreased VEGF levels and was adjusted by weeks of gestation (WG) in our model. In the longitudinal study, 7/12 patients developed PE. VEGF produced by PBMCs cells was significantly lower in PE at 24-26 WG.
  
  
  CONCLUSIONS
  VEGF production by PBMCs is inhibited during PE, creating a downregulation of the microenvironment; this deficiency may contribute to the pathogenesis of disease.
authors.affiliation: Unidad de Investigación Médica en Medicina Reproductiva, UMAE Hospital de Ginecología y Obstetricia No. 4 "Luis Castelazo Ayala", Instituto Mexicano del Seguro Social (IMSS), México, D.F., México; Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, UMAE Hospital de Pediatría, "Dr. Silvestre Frenk Freund", CMN Siglo XXI, IMSS, México, D.F., México. Electronic address: carlupita@yahoo.com.mx.
authors.forename: María G
authors.initials: MG
authors.lastname: Cardenas-Mondragon
authors.affiliation: Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, UMAE Hospital de Pediatría, "Dr. Silvestre Frenk Freund", CMN Siglo XXI, IMSS, México, D.F., México; Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, México, D.F., México.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Vallejo-Flores
authors.affiliation: Departamento de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, México, D.F., México.
authors.forename: Jose
authors.initials: J
authors.lastname: Delgado-Dominguez
authors.affiliation: Servicio de Complicaciones Hipertensivas del Embarazo, UMAE Hospital de Ginecología y Obstetricia No. 4 "Luis Castelazo Ayala", IMSS, México, D.F., México.
authors.forename: Juan F
authors.initials: JF
authors.lastname: Romero-Arauz
authors.affiliation: Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, UMAE Hospital de Pediatría, "Dr. Silvestre Frenk Freund", CMN Siglo XXI, IMSS, México, D.F., México.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Gomez-Delgado
authors.affiliation: Unidad de Investigación en Salud en el Trabajo, CMN Siglo XXI, IMSS, México, D.F., México.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Aguilar-Madrid
authors.affiliation: Dirección de Investigación Operativa en Epidemiología, Dirección General de Epidemiología, Secretaria de Salud, México, D.F., México.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Sanchez-Barriga
authors.affiliation: Unidad de Investigación Médica en Medicina Reproductiva, UMAE Hospital de Ginecología y Obstetricia No. 4 "Luis Castelazo Ayala", Instituto Mexicano del Seguro Social (IMSS), México, D.F., México; Servicio de Complicaciones Hipertensivas del Embarazo, UMAE Hospital de Ginecología y Obstetricia No. 4 "Luis Castelazo Ayala", IMSS, México, D.F., México.
authors.forename: Janeth
authors.initials: J
authors.lastname: Marquez-Acosta
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D015536:Down-Regulation; D005260:Female; D005865:Gestational Age; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008137:Longitudinal Studies; D011225:Pre-Eclampsia / Q000097:blood / Q000378:metabolism*; D011247:Pregnancy; D011507:Proteinuria / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000097:blood; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: Hypertensive disorders of pregnancy; Preeclampsia; VEGF; sFlt-1