Abstract
Pre-eclampsia is the most common pregnancy complication affecting 1 in 20 pregnancies, characterized by high blood pressure and signs of organ damage, most often to the liver and kidneys. Metabolic network analysis of published lipidomic data points to a shortage of Coenzyme A (CoA). Gene expression profile data reveal alterations to many areas of metabolism and, crucially, to conflicting cellular regulatory mechanisms arising from the overproduction of signalling lipids driven by CoA limitation. Adverse feedback loops appear, forming sphingosine-1-phosphate (a cause of hypertension, hypoxia and inflammation), cytotoxic isoketovaleric acid (inducing acidosis and organ damage) and a thrombogenic lysophosphatidyl serine. These also induce mitochondrial and oxidative stress, leading to untimely apoptosis, which is possibly the cause of CoA restriction. This work provides a molecular basis for the signs of pre-eclampsia, why polycystic ovary syndrome is a risk factor and what might be done to treat and reduce the risk of disease.
Highlights
Pre-eclampsia is a significant cause of maternal and foetal morbidity and mortality, accounting for at least 63,000 maternal deaths per annum [1]
This work has studied pre-eclampsia by examining data from molecular up to population scales. It points to a shortage of Coenzyme A (CoA) as a feature leading to the production of signalling lipids and toxic metabolites that induce vasoconstriction, inflammation, oxidative stress, thrombogenesis, acidosis, apoptosis and neurotoxicity
14 were either signalling molecules or markers/agents of adverse physiological conditions found in pre-eclampsia, such as 2-hydroxybutanoate and oxo-methylbutanoic acid (Table 1)
Summary
Pre-eclampsia is a significant cause of maternal and foetal morbidity and mortality, accounting for at least 63,000 maternal deaths per annum [1]. Proteomics data are less useful because disruption of the syncytiotrophoblast results in intracellular proteins masking any potential signalling molecules [3] This makes interpretation of biomarkers in common between PCOS and PE difficult to interpret [6]. This work has studied pre-eclampsia by examining data from molecular up to population scales It points to a shortage of Coenzyme A (CoA) as a feature leading to the production of signalling lipids and toxic metabolites that induce vasoconstriction, inflammation, oxidative stress, thrombogenesis, acidosis, apoptosis and neurotoxicity. It explains why PCOS is a risk factor for PE and points to potential treatments plus areas for further investigation
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