الفهرس 
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Abstract
Preeclampsia is pregnancy specific syndrome which is characterized by new onset of hypertension and proteinuria and is considered as a significant cause of maternal and neonatal mortality. Although it is considered to affect about 8% of all pregnancies
Although the pathophysiology of preeclampsia remains unclear placental ischemia is widely regarded as a key factor as a result of poor placentation and inadequate trophoblastic invasion which are associated with obstructive lesion of the spiral arteries called acute atherosis, lead to placental ischemia. This placental ischemia causes preeclampsia.
An important item in the management is early detection of the condition which is considered as a life saving and important courner stone in the management. Early detection is through with maternal serum markers.
Vascular tone is maintained by a balance between vasodilator and vasoconstrictor mediators. The release of biologically active factors in response to placental hypoxia/ischemia could result in EC and VSM dysfunction and influence the release of various vascular mediators. The EC dysfunction could also involve changes in the release of vasodilators, such as NO, prostacyclin (PGI2), and endothelium-derived hyperpolarizing factor (EDHF), or vasoconstrictor mediators, such as ET-1 and AngII in human
Maternal plasma VEGF increases before the clinical onset of PE and is further elevated during the vasoconstriction phase of the disease.
VEGF normally acts as a vasodilator patients receiving VEGF antagonists for cancer treatments develop HTN, proteinuria and endothelial activation
Placental growth factor (PlGF) may cause vasodilation in the peripheral vasculature and, thereby, modulates regional blood flow and vascular resistance. During Norm-Preg, circulating PlGF concentrations are more than 40 times greater than VEGF, but PlGF has only 1/10th the affinity for the Flt-1 receptor compared to VEGF. During PE, circulating PlGF levels decrease whiles the levels of its antagonist protein; sFlt-1 are increase.
Because the sFlt-/PlGF concentration ratio is much higher in PE than Norm-Preg women as early as the second trimester, it can be used as an early indicator of the onset of PE.
Soluble FMS-like tyrosine kinase-1 (sFlt-1) is a VEGF and PlGF antagonist protein that binds VEGF and PlGF and prevents their interaction with their endogenous receptors.
Compared with Norm-Preg women, circulating levels of sFlt-1 are increased in PE women secondary to placental ischemia/hypoxia.
The increase in sFlt-1 paired with a decrease in VEGF and PlGF promote proteinuria, HTN, and glomerular endotheliosis, the hallmarks of PE.
Endoglin is a transmembrane receptor for transforming growth factor-β (TGF-β) that is expressed on ECs. Placenta-derived soluble endoglin (sEng) is an anti-angiogenic protein with a potential role in PE. sEng inhibits TGF-β1 signaling in ECs and blocks TGF-β1 mediated activation of eNOS and vasodilation, suggesting that dysregulated TGF-β signaling is involved in the pathogenesis of PE.
sEng is elevated in sera of PE women 2 to 3 months before the onset of clinical signs, correlates with the severity of PE, and falls after delivery. Thus, an increase in the serum level of sEng together with increased sFlt-PlGF ratio could be predictive of PE.
However, the use of sFlt-1 and sEng as mediators or predictors of PE should be viewed with extreme caution as the levels of sFlt-1 and sEng may not be altered in some women or experimental animals with PE/HTN-Preg as compared to Norm-Preg.
Cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-8, are involved in cell proliferation and hypoxia-mediated cell activation. Hypoxia induces marked increases in IL-6 and IL-8 synthesis in VSM cells.Reduction of Uterine Perfusion Pressure during pregnancy and the ensuing placental ischemia are thought to increase the release of TNF-α and IL-6 into the maternal circulation, leading to EC dysfunction, generalized vascular changes and HTN.
The plasma levels of TNF-α and IL-6 are elevated in women with PE. In contrast, IL-10, which may be involved in the maintenance of pregnancy by inducing corpus luteum maturation and progesterone production, is decreased in PE women.
Hypoxia promotes the induction of hypoxia inducible factors (HIF)-1α and HIF-1β, which are quickly degraded after reoxygenation. Once it is produced, HIF-1 binds to the enhancer region of genes that encode glycolytic enzymes and VEGF. Because placental hypoxia likely plays a role in PE, the role of HIFs in the human placenta has been investigated. The expression of HIF-1α and HIF-2α, but not HIF-1β, is selectively increased in PE placenta. Upregulation of HIF-1 also enhances the expression of VEGF.