Identification of Biomarkers for Preeclampsia Based on Metabolomics

Abstract

Background: Preeclampsia (PE) is a significant cause of maternal and neonatal morbidity and mortality worldwide. However, the pathogenesis of PE is unclear and reliable early diagnostic methods are still lacking. The purpose of this review is to summarize potential metabolic biomarkers and pathways of PE, which might facilitate risk prediction and clinical diagnosis, and obtain a better understanding of specific metabolic mechanisms of PE. Methods: This review included human metabolomics studies related to PE in the PubMed, Google Scholar, and Web of Science databases from January 2000 to November 2021. The reported metabolic biomarkers were systematically examined and compared. Pathway analysis was conducted through the online software MetaboAnalyst 5.0. Results: Forty-one human studies were included in this systematic review. Several metabolites, such as creatinine, glycine, L-isoleucine, and glucose and biomarkers with consistent trends (decanoylcarnitine, 3-hydroxyisovaleric acid, and octenoylcarnitine), were frequently reported. In addition, eight amino acid metabolism-related, three carbohydrate metabolism-related, one translationrelated and one lipid metabolism-related pathways were identified. These biomarkers and pathways, closely related to renal dysfunction, insulin resistance, lipid metabolism disorder, activated inflammation, and impaired nitric oxide production, were very likely to contribute to the progression of PE. Conclusion:This study summarized several metabolites and metabolic pathways, which may be associated with PE. These highfrequency differential metabolites are promising to be biomarkers of PE for early diagnosis, and the prominent metabolic pathway may provide new insights for the understanding of the pathogenesis of PE.

Targeted Metabolomics Revealed a Sex-Dependent Signature for Metabolic Syndrome in the Mexican Population

“…The increased con-centrations of BCAAs overload the catabolic pathways in the liver and skeletal muscle, increasing the production of succinyl-CoA and propionyl-CoA, reducing the β-oxidation of fatty acids and the catabolism of glucose. Therefore, the loss of efficiency in oxidative metabolic pathways amplifies the oxidation of partially oxidized products, increasing mitochondrial stress, reducing insulin sensitivity, and altering circulating glucose concentrations [59,60]. In the present study, men under 45 years diagnosed with MetS have the highest concentrations of BCAAs and proline.…”

Circulating Growth Differentiation Factor 15 and Preeclampsia: A Meta-Analysis

“…Moreover, women with preeclampsia are associated with higher risk of life-time adverse cardiovascular events 8 . Due to the adverse maternal and infantile outcomes related with preeclampsia, continuous efforts have been made to identify possible biomarkers which could predict the incidence of preeclampsia 9 .…”

Blood biomarkers representing maternal-fetal interface tissues used to predict early-and late-onset preeclampsia but not COVID-19 infection

“…Both EZH2 and PLOD2 are involved in lysine degradation respectively resulting in carnitine-glycine and protein 5-galactosyloxylysine as either end or side products. We could find no evidence for an association of the latter with preeclampsia, but a systematic review identified carnitine-related metabolites and glycine as metabolomics associated with preeclampsia [68] . Notably, acyl carnitine and glycine were significantly higher in preeclamptic women and cord blood, respectively, compared to normotensive controls and maternal blood; however, these did not individually predict preeclampsia [69] .…”