Inositol Phosphoglycan P-Type in Preeclampsia

Abstract

Abstract-A state of insulin resistance has been demonstrated in active preeclampsia, and women with clinical evidence of insulin resistance are at higher risk to develop this syndrome during pregnancy. Recently, inositol phosphoglycan P-type, a putative second messenger of insulin action, has been implicated in the pathophysiology of preeclampsia and is increased in the placenta, amniotic fluid, and maternal urine of preeclamptic women compared with normal pregnant women. We report here a case-control study to assess the potential of urinary levels of inositol phosphoglycan P-type as a screening test for preeclampsia. Twenty-seven preeclamptic women and 47 healthy pregnant women were recruited. A polyclonal antibody-based ELISA was developed to detect levels of inositol phosphoglycan P-type in urine. Its content in urinary specimens was found to be 30-fold higher in preeclamptic subjects than control subjects (329.1Ϯ21.8 versus 9.2Ϯ1.5; PϽ0.001), with a higher level in all of the preeclamptic cases. For 6 women who developed preeclampsia, Ͼ1 gestational date sample of urine was available, and retrospective analysis showed a significant time-related increase of the urinary level of inositol phosphoglycan P-type Յ7 weeks before clinical diagnosis of preeclampsia. Urinary level of inositol phosphoglycan P-type increased after diagnosis indicating a possible pathophysiological threshold level and steeply decreased after delivery. Key Words: preeclampsia Ⅲ screening test Ⅲ inositol phosphoglycan Ⅲ biological marker Ⅲ insulin resistance P reeclampsia (PE) represents the most severe form of hypertensive disorder of human pregnancy being associated with a substantial maternal and perinatal morbidity and mortality. 1 It affects Ϸ5% of all pregnancies, although its causes remain unclear. A state of insulin resistance has been demonstrated in active PE, 2,3 and women with clinical evidence of insulin resistance are at higher risk of developing this syndrome during pregnancy. 4 Recently, a family of putative insulin mediators, inositol phosphoglycans (IPGs), have been implicated in the pathophysiology of PE. A high concentration of bioactive IPG P-type (P-IPG) was found in human preeclamptic placenta, 5 urine, and amniotic fluid. 6 Further studies have provided evidence of insulin resistance in human placentas from preeclamptic pregnancies and demonstrated an association between P-IPG and the insulin signaling cascade. 7 IPGs have been demonstrated to exert insulin-mimetic activity in both glucose and lipid metabolism mainly through the activation of pyruvate dehydrogenase phosphatase, glycogen synthase phosphatase, and glycerol-3-phosphate acyltransferase. 8,9 The elevated concentration of glycogen in terminal villi from preeclamptic placentas, because of an increased activity of glycogen synthase, 10 may be a consequence of the abnormal content of P-IPG in the placentas of preeclamptic patients.In this report, we focus our attention on the urinary excretion of IPGs using a novel assay specifically developed to analyze uri...

An essay of reflection: Why does preeclampsia exist in humans, and why are there such huge geographical differences in epidemiology?

“…Second, and this a point where we want to create a debate, for 15 years now (Kunjara et al, 2000;Williams et al, 2007;Scioscia et al, 2014), there has been evidence that the detection of the presence of inositol -phosphoglycans type P (IPG-P) in pregnant women's urine is strongly specific to preeclampsia, and correlates absolutely with proteinuria. However, IPG-P appears 2-7 weeks before the onset of clinical disease.…”

“…• Role of hyperglycosylated HCG (deepness of implantation) (Cole et al, 2008) • Immunological animal model for PE (Ahmed, Girardi et al, workshop 2008, published 2010 • Pivotal role of Treg cells (≈2010s) (Clark and Chaouat, 2012) Rademacher, London University) to the discovery of IPG-P (Kunjara et al, 2000;Williams et al, 2007;Scioscia et al, 2014). Finally, and to come back to pravastatin, current trials are ongoing in areas with predominant LOP.…”

Recent Progress Toward the Understanding of the Pathophysiology of Hypertension During Preeclampsia

“…[93][94][95][96][97][98][99][100][101][102][103][104][105][106][107][108][109][110][111] Recent studies have indicated a relationship between elements of the metabolic syndrome such as elevated serum triglycerides and free fatty acids, insulin resistance, and glucose intolerance and the occurrence of preeclampsia. [93][94][95][96][97][98][99][100][101][102][103][104][105][106][107][108][109][110][111] In fact, several authors have suggested insulin resistance may presage the manifestation of preeclampsia, 98 -105 whereas Thadhani et al have proposed that insulin resistance during pregnancy may interact with other conditions such as impaired angiogenesis to generate a preeclamptic phenotype. 101 Although plasma levels of lipids are increased during normal pregnancy, plasma concentrations of both triglyceride-rich lipoproteins and nonesterified fatty acids are significantly increased in women that develop preeclampsia relative to normal pregnant women.…”

Débats actuels sur l’immunologie de la prééclampsie. Comptes rendus du sixième colloque international de La Réunion (décembre 2008)

“…Ces facteurs antiangiogéniques circulants pourraient s'intégrer au modèle proposé en 1993 par David Haig (Harvard, États-Unis) de conflit génétique maternofoetal [48] comme le reflet d'une stratégie de sauvetage foetal. De même, les inositol phosphoglycans-P [IPG-P] (présentés dans différents colloques par Rademacher, Londres, GB, et Scioscia, Vérone, Italie) pourraient représenter l'équivalent métabolique d'un signal de détresse foetal et participer à l'inflammation endothéliale [49]. La preuve définitive de l'implication de ces médiateurs bioactifs laisse espérer la mise au point de thérapeutiques du syndrome maternel dans un futur très proche (moins d'une décennie).…”