Mazzarelli, Laura Letizia (2010) The role of apoptosis in pregnancies complicated by Pre-eclampsia and IUGR. [Tesi di dottorato] (Unpublished)

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Pregnancy complications such as preeclampsia, intrauterine growth retardation (IUGR), preterm labor affect a considerable number of pregnancies and account for significant perinatal morbidity and mortality. Although the pathophysiology has not been clearly defined, the common phenomenon observed between these diseases is abnormal development and function of the placenta. In complicated pregnancies such as preeclampsia or IUGR, a greater incidence of trophoblast apoptosis has been observed, suggesting that alterations in the regulation of trophoblast apoptosis may contribute to the pathophysiology of these diseases. We evaluate morphogenetic alterations of placenta and apoptosis of trophoblast into placenta of pregnancies with preeclampsia/intrauterine growth restriction and controls. Trophoblast’s apoptosis into placenta was quantified evaluating bcl-2 apoptosis marker. Placental’s morphogenetic alterations was evaluated with HGF/c-met/STAT3 cascade. Placental ischemia is thought to develop as a result of this abnormal cytotrophoblastic invasion; this has been proposed as leading to release of placental factors and imbalance of angiogenic factors, causing the widespread endothelial dysfunction. Endothelial dysfunction is characterized by a fall in production and activity of vasodilator prostaglandins, especially prostacyclin and nitric oxide with a raised ratio of thromboxane A2 to prostacyclin that reduces uteroplacental blood flow and the blood supply to the fetus. One of the most important regulator of endothelial function is the adrenergic system. Endothelial cells express on their surface the β2-adrenergic receptors (β2AR) that are involved in the regulation of vascular tone throughthe release of oxide nitric (NO). An impairment in β2AR-mediated vasodilatation has been described in both animals and human models of hypertension. Recently it is been reported the important role of some proteins (G-protein coupled receptor kinases-GRKs) involved in the desensitization and down-regulation of β2AR in the pathogenesis of hypertension. In this paper we have analyzed the role of the most important GRK expressed in cardiovascular system (βAK 1 or GRK2) in umbilical artery (UA)of preeclamptic patients and normotensive pregnant women to characterize its eventual role in the pathogenesis of preeclampsia and related clinical syndromes, such as gestational hypertension (GH) and fetal growth restriction (FGR). We also evaluated if there are some protective factors against preeclampsia. In fact, women with a thalassemic trait seems to be protecte against preeclampsia.

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