Abstract
Placental growth factor (PlGF) is an angiogenic factor identified in the maternal circulation, and a key biomarker for the diagnosis and management of placental disorders. Furthermore, enhancing the PlGF pathway is regarded as a promising therapy for preeclampsia. The source of PlGF is still controversial with some believing it to be placental in origin while others refute this. To explore the source of PlGF, we undertook a prospective study enrolling normal pregnant women undergoing elective caesarean section. The level of PlGF was estimated in 17 paired serum samples from the uterine vein (ipsilateral or contralateral to the placental insertion) during caesarean section and from a peripheral vein on the same day and second day post-partum. PlGF levels were higher in the uterine than in the peripheral vein with a median difference of 52.2 (IQR 20.1–85.8) pg/mL p = 0.0006. The difference when the sampled uterine vein was ipsilateral to the placenta was 54.8 (IQR 37.1–88.4) pg/mL (n = 11) and 23.7 (IQR −11; 70.5) pg/mL (n = 6) when the sample was contralateral. Moreover, PlGF levels fell by 83% on day 1–2 post-partum. Our findings strongly support the primary source of PlGF to be placental. These findings will be of value in designing target therapies such as PlGF overexpression, to cure placental disorders during pregnancy.
Highlights
Placental growth factor (PlGF) is an angiogenic factor identified in the maternal circulation, and a key biomarker for the diagnosis and management of placental disorders
The median difference between PlGF uterine and peripheral vein concentrations was 52.2 (IQR 20.1–85.8) pg/mL, being 23.7 (IQR −11; 70.5) pg/ml when the uterine vein (UV) sample was contralateral to the placenta (n = 6; paired Wilcoxon test p = 0.12) and 54.8 (IQR 37.1–88.4) pg/mL when the UV sample was ipsilateral to the placenta (n = 11; paired Wilcoxon test p = 0.003) (Fig. 2)
PlGF is an angiogenic factor that belongs to the vascular endothelial growth factor (VEGF) family
Summary
Placental growth factor (PlGF) is an angiogenic factor identified in the maternal circulation, and a key biomarker for the diagnosis and management of placental disorders. The level of PlGF was estimated in 17 paired serum samples from the uterine vein (ipsilateral or contralateral to the placental insertion) during caesarean section and from a peripheral vein on the same day and second day post-partum. There is discrepancy in the literature as to whether the placenta is a significant source of maternal circulating PlGF in normal pregnancies. Previous studies have examined in vivo PlGF placental production by interrogating the PlGF concentration gradient between the uterine vein (closer to placenta) and a peripheral vein. Whilst a difference has been shown by one group[8,10], implicating the placenta as a main source of PlGF, this was not shown by another[9]. We aimed to determine if the placenta is the primary source of PlGF in normal pregnancies in vivo. We optimized previous conditions by using an automated assay with a low coefficient of variation, interrogating patients with lateral placentas, as well as making a comparison with postpartum peripheral levels
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