Measurement of vasoactive metabolites (hydroxyeicosatetraenoic and epoxyeicosatrienoic acids) in uterine tissues of normal and compromised human pregnancy

Abstract

Increased production of 5-HETE, 12-HETE and 15-HETE metabolites in preeclamptic placentae indicates an important role for this family of eicosanoids in the cause of this disease.

Applications of metabolomics in the study and management of preeclampsia: a review of the literature

“…Biag et al (Baig, Lim, Fernandis, Wenk, Kale, Su, Biswas et al 2013) reported that dysregulation of lipid metabolism was evident in the placental syncytiotrophoblast microvesicles of women with preeclampsia and those with recurrent miscarriage relative to controls, and specifically that levels of sphingomyelin and phosphatidylserine were increased while phosphatidylinositol. Similarly Pearson et al (Pearson, Zhang, Arya, Warren, Ortori, Fakis, Khan et al 2010) observed dysregulation of vasoactive metabolites in women undergoing cesarean due to preeclampsia or a growth restricted pregnancy, relative to elective cesareans. These findings are not unexpected given the strong correlation between these disorders and preeclampsia, and further work is required to disentangle the shared and distinct metabolic dysregulation underlying these conditions, and particularly the role that lipid metabolism may be playing.…”

“…Blood plasma was the most commonly used biologic media (n = 10) (Bahado-Singh, Akolekar, Mandal, Dong, Xia, Kruger, Wishart et al 2012; De Oliveira, Câmara, Bonetti, Turco, Bertolla, Moron, Sass et al 2012; Kelly, Croteau-Chonka, Dahlin, Mirzakhani, Wu, Wan, McGeachie et al 2016; Kenny, Broadhurst, Dunn, Brown, North, McCowan, Roberts et al 2010; Kenny, Dunn, Ellis, Myers, Baker, Kell 2005; Odibo, Goetzinger, Odibo, Cahill, Macones, Nelson, Dietzen 2011; Pinto, Almeida, Martins, Duarte, Barros, Galhano, Pita et al 2015; Schott, Hahn, Kurbacher, Moka 2012; Turner, Brewster, Simpson, Walker, Fisher 2007; Turner, Brewster, Simpson, Walker, Fisher 2008), followed by serum (n = 7) (Bahado-Singh, Akolekar, Mandal, Dong, Xia, Kruger, Wishart et al 2013; Bahado-Singh, Syngelaki, Akolekar, Mandal, Bjondahl, Han, Dong et al 2015; Chen, He, Tan, Xu 2017; Kenny, Broadhurst, Brown, Dunn, Redman, Kell, Baker 2008; Koster, Vreeken, Harms, Dane, Kuc, Schielen, Hankemeier et al 2015; Kuc, Koster, Pennings, Hankemeier, Berger, Harms, Dane et al 2014), and placental or intrauterine tissue samples (n = 7) (Austdal, Thomsen, Tangerås, Skei, Mathew, Bjørge, Austgulen et al 2015; Baig, Lim, Fernandis, Wenk, Kale, Su, Biswas et al 2013; Dunn, Brown, Worton, Davies, Jones, Kell, Heazell 2012; Jain, Jayasimhulu, Clark 2004; Korkes, Sass, Moron, Câmara, Bonetti, Cerdeira, Da Silva et al 2014; Pearson, Zhang, Arya, Warren, Ortori, Fakis, Khan et al 2010; Sohlberg, Wikström, Olovsson, Lindgren, Axelsson, Mulic-Lutvica, Weis et al). The remaining studies used urine (n = 1) (Diaz, Barros, Goodfellow, Duarte, Galhano, Pita, Almeida et al 2013), urine and serum (n = 2) (Austdal, Skråstad, Gundersen, Austgulen, Iversen, Bathen 2014; Austdal, Tangerås, Skråstad, Salvesen, Austgulen, Iversen, Bathen 2015), or breast milk (n=1) (Dangat, Upadhyay, Kilari, Sharma, Kemse, Mehendale, Lalwani et al 2016).…”

“…Sixteen studies performed metabolic profiling with Mass Spectrometry (MS), while 12 used a form of nuclear magnetic resonance spectroscopy (NMR). Ten studies were targeted or semi-targeted to the measurement of specific groups of metabolites (Baig, Lim, Fernandis, Wenk, Kale, Su, Biswas et al 2013; Braekke, Ueland, Harsem, Karlsen, Blomhoff, Staff 2007; Jain, Jayasimhulu, Clark 2004; Koster, Vreeken, Harms, Dane, Kuc, Schielen, Hankemeier et al 2015; Kuc, Koster, Pennings, Hankemeier, Berger, Harms, Dane et al 2014; Odibo, Goetzinger, Odibo, Cahill, Macones, Nelson, Dietzen 2011; Pearson, Zhang, Arya, Warren, Ortori, Fakis, Khan et al 2010; Pinto, Maciel, Melo, Domingues, Galhano, Pita, Almeida et al 2014; Schott, Hahn, Kurbacher, Moka 2012; Sohlberg, Wikström, Olovsson, Lindgren, Axelsson, Mulic-Lutvica, Weis et al). The number of metabolites measured differed according to the choice of technology and approach.…”

“…The chosen technology also dictated the reporting of results to an extent. The level of quantitative detail varied between the studies, and a number of the non-biomarker studies (De Oliveira, Câmara, Bonetti, Turco, Bertolla, Moron, Sass et al 2012; Jain, Jayasimhulu, Clark 2004; Korkes, Sass, Moron, Câmara, Bonetti, Cerdeira, Da Silva et al 2014; Pearson, Zhang, Arya, Warren, Ortori, Fakis, Khan et al 2010; Schott, Hahn, Kurbacher, Moka 2012; Sohlberg, Wikström, Olovsson, Lindgren, Axelsson, Mulic-Lutvica, Weis et al ; Turner, Brewster, Simpson, Walker, Fisher 2007; Turner, Brewster, Simpson, Walker, Fisher 2008) did not report effect sizes for individual or groups of metabolites, but rather commented on general trends observed in the results. This was particularly common among the NMR studies which often reported spectral regions rather than actual metabolites.…”

Molecular Mechanisms Regulating the Vascular Prostacyclin Pathways and Their Adaptation during Pregnancy and in the Newborn

“…In PE, other bioactive factors such as sFlt-1 and other eicosanoids such as HETEs and isoprostanes are increased (Walsh et al, 2000;Pearson et al, 2010). In addition, deficient 15-deoxy-PGJ 2 /PPAR␥-signaling may be involved in the initial abnormal placentation in PE (Helliwell et al, 2004b).…”