Serum Levels of Macrophage Colony Stimulating, Vascular Endothelial, and Placenta Growth Factor in Relation to Later Clinical Onset of Pre-Eclampsia and a Small-for-Gestational Age Birth

Impaired placental angiogenesis is implicated in the pathophysiology of small for gestational age (SGA) infants. Placental expression of vascular endothelial growth factor (VEGF), a potent angiogenic factor, is reduced in SGA pregnancies. We aimed to evaluate the association of two single nucleotide polymorphisms (SNPs, VEGF-2578C/A and VEGF+936C/T) in VEGF gene which reduce VEGF expression, in SGA pregnancies andexamine their effects on first trimester placental VEGF expression. 3196 nulliparous pregnant women, their partners and babies were recruited in Adelaide and Auckland to a prospective multicentre cohort study (SCOPE Study). Amongst 2123 Caucasian women, 216 (11.9%) delivered a SGA infant defined as <10th customised centile. Uncomplicated Caucasian pregnancies served as controls (n = 1176). Uterine and umbilical artery Doppler velocimetry was performed at 20 weeks gestation. DNA extracted from peripheral blood from couples and cord blood from babies was genotyped using Sequenom MassARRAY. 74 first trimester placentae collected from elective terminations of pregnancy were genotyped for the same SNPs and the VEGF expression determined by RT-PCR. Neonatal VEGF+936 CT+TT genotypes associate with SGA (OR 1.6, 95%CI 1.1–2.3), lower birthweight (P = 0.005), customised birthweight centile (p=0.03), lower placental weight (P = 0.04) and an increased uterine artery resistance index (RI, P = 0.004). Maternal VEGF+936 CT+TT associate with bilateral notching of the uterine artery waveform (OR 1.4, 95%CI 1.0–1.8) and an increased umbilical artery RI (OR 1.5, 95%CI 1.1–2.1). VEGF+936 CT first trimester placentae have lower VEGF expression compared to CC (P = 0.045). Neonatal VEGF-2578 AA associates with bilateral uterine artery notching (OR 1.5, 95%CI 1.1–2.2) and increased umbilical artery RI (OR 1.6, 95%CI 1.0–2.6). Maternal VEGF-2578 CA+AA associate with increased umbilical artery RI (OR 1.5, 95%CI 1.0–2.2). VEGF polymorphisms reduce first trimester VEGF expression and associate with increased resistance in the placental circulation suggesting impaired placental function. VEGF+936 SNP confers increased risk for SGA.

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Serum Levels of Three Angiogenic Factors in Systemic Lupus Erythematosus and Their Clinical Significance

BioMed Research International ◽

10.1155/2014/627126 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 11

Author(s):

Ling Zhou ◽

Guoyuan Lu ◽

Lei Shen ◽

Linfeng Wang ◽

Mingjun Wang

Keyword(s):

Growth Factor ◽

Lupus Erythematosus ◽

Serum Levels ◽

Angiogenic Factors ◽

Vascular Endothelial ◽

Healthy Controls ◽

Placenta Growth Factor ◽

Sledai Score ◽

Endothelial Growth Factor ◽

Normal Controls

Our research investigates the serum levels of three angiogenic factors in the AF family, namely, placenta growth factor (PlGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF), in 54 patients with SLE (SLE group) and 28 healthy controls (normal control) through ELISA measurement. And their interrelationships were also systematically analyzed. The SLE patients were then divided into active SLE group and inactive SLE group according to the SLEDAI score. The results show that serum levels of PlGF, bFGF, and VEGF in all SLE group and active SLE group were higher than those in normal controls. Serum levels of PlGF and bFGF in inactive SLE group were higher than those in normal controls. The level of PlGF was positively correlated with VEGF in SLE patients and positive correlation is also shown in bFGF with VEGF. The levels of PlGF and VEGF in SLE patients were positively correlated with both ESR and SLEDAI score. Thus a tentative conclusion can be drawn that the serum levels of the angiogenic factors, for example, PlGF, bFGF, and VEGF, may be relevant in the pathogenesis of SLE, and the concentrations of PlGF and VEGF seem to be the markers of SLE activity.

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