FKBPL and SIRT-1 Are Downregulated by Diabetes in Pregnancy Impacting on Angiogenesis and Endothelial Function.

Diabetes in pregnancy is associated with adverse pregnancy outcomes including preterm birth. Although the mechanisms leading to these pregnancy complications are still poorly understood, aberrant angiogenesis and endothelial dysfunction play a key role. FKBPL and SIRT-1 are critical regulators of angiogenesis, however, their roles in pregnancies affected by diabetes have not been examined before in detail.

Role of A Novel Angiogenesis FKBPL-CD44 Pathway in Preeclampsia Risk Stratification and Mesenchymal Stem Cell Treatment.

Context: Preeclampsia is a leading cardiovascular complication in pregnancy lacking effective diagnostic and treatment strategies.

Objective: To investigate the diagnostic and therapeutic target potential of the angiogenesis proteins, FK506-binding protein like (FKBPL) and CD44.

Design And Intervention: FKBPL and CD44 plasma concentration or placental expression were determined in women pre- or postdiagnosis of preeclampsia.

Placental vascularization indices and prediction of pre-eclampsia in high-risk women.

Objective: To assess ability of first and second trimester Placental Vascularization Indices (PVIs) to predict pre-eclampsia (PE) in high-risk pregnancies.

Method: PVIs derived from 3-Dimensional power Doppler imaging were measured at 11+0-13 + 6 (n = 194) and 19+0-21 + 6 weeks (n = 195). Logistic regression (LR) models used PE as the outcome.

The endogenous anti-angiogenic family of splice variants of VEGF, VEGFxxxb, are down-regulated in pre-eclamptic placentae at term.

PET (pre-eclamptic toxaemia) has recently been linked with alterations in production of a VEGFR1 [VEGF (vascular endothelial growth factor) receptor 1] splice variant that acts as a circulating inhibitor. We have recently described a family of naturally occurring splice variants of VEGF, termed VEGFxxxb, that also appear to act as inhibitors of conventional VEGFxxx-mediated angiogenesis. To determine whether alteration in splicing of VEGF-VEGFR family members extended beyond VEGFR1, we investigated the effect of pre-eclampsia on placental VEGFxxxb mRNA and protein expression.

Soluble vascular endothelial growth factor receptor-1 (sFlt-1) is increased throughout gestation in patients who have preeclampsia develop.

Objective: This study was undertaken to analyze prospectively circulating vascular endothelial growth factor (VEGF) and its soluble receptor, (s) Flt-1, throughout normotensive and preeclamptic pregnancies and to assess the importance of these proteins in the development of preeclampsia.

Study Design: In this longitudinal cohort study, serum samples were collected from recruited subjects throughout pregnancy at 12, 20, 30, and 37 weeks and in the 24 hours before and after delivery. Subjects were divided retrospectively into normotensive and preeclamptic groups.

Plasma from women with severe pre-eclampsia increases microvascular permeability in an animal model in vivo.

Pre-eclampsia results in oedema, hypertension and proteinuria, and is associated with increased vascular permeability. A number of studies have pointed to the existence of a circulating macromolecule that induces this endothelial dysfunction. To test whether this circulating factor could increase vascular permeability, we have measured the effect of dialysed human plasma from pregnant women with mild or severe pre-eclampsia (pre-eclamptic toxaemia).