María G Cardenas-Mondragon1, Gabriela Vallejo-Flores2, Jose Delgado-Dominguez3, Juan F Romero-Arauz4, Alejandro Gomez-Delgado5, Guadalupe Aguilar-Madrid6, Juan J Sanchez-Barriga7, Janeth Marquez-Acosta8. 1. 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. 2. 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. 3. Departamento de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, México, D.F., México. 4. Servicio de Complicaciones Hipertensivas del Embarazo, UMAE Hospital de Ginecología y Obstetricia No. 4 "Luis Castelazo Ayala", IMSS, México, D.F., México. 5. 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. 6. Unidad de Investigación en Salud en el Trabajo, CMN Siglo XXI, IMSS, México, D.F., México. 7. Dirección de Investigación Operativa en Epidemiología, Dirección General de Epidemiología, Secretaria de Salud, México, D.F., México. 8. 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.
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.
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: Olivia K Travis; Dakota White; W Austin Pierce; Ying Ge; Cassandra Y Stubbs; Frank T Spradley; Jan M Williams; Denise C Cornelius Journal: Physiol Rep Date: 2019-04