Plasma metabolic profile reveals signatures of maternal health during gestational hypertension and preeclampsia without and with severe features

Author(s)

Kaihara, Julyane N. S. ; de Moraes, Fabio Rogerio ; Nunes, Priscila Rezeck ; Alves, Marco G. ; Cavalli, Ricardo C. ; Tasic, Ljubica ; Sandrim, Valeria Cristina

• Document type: Journal article
• Source: PLoS One; v. 19, n. 11, p. 22-pg., 2024-11-26.

Abstract

Preeclampsia, a pregnancy-specific syndrome, poses substantial risks to maternal and neonatal health, particularly in cases with severe features. Our study focuses on evaluating the impact of low molecular weight metabolites on the intricate mechanisms and pathways involved in the pathophysiology of preeclampsia when severe features are present. We aim to pinpoint the distinct metabolomic profile in maternal plasma during pregnancies affected by hypertensive disorders and to correlate the metabolite levels with the clinical characteristics of the study cohort. A total of 173 plasma samples were collected, comprising 36 healthy pregnant women (HP), 52 patients with gestational hypertension (GH), 43 with preeclampsia without (PE-), and 42 with severe features (PE+). Nuclear magnetic resonance spectroscopy and metabolite identification were conducted to establish the metabolomic profiles. Univariate and chemometric analyses were conducted using MetaboAnalyst, and correlations were performed using GraphPad Prism. Our study unveils distinct metabolomic profiles differentiating HP women, patients featuring GH, and patients with PE-and PE+. Our analysis highlights an increase in acetate, N,N-dimethylglycine, glutamine, alanine, valine, and creatine levels in the PE+ group compared to the HP and GH groups. The PE+ group exhibited higher concentrations of N,N-dimethylglycine, glutamine, alanine, and valine compared to the PE-group. Moreover, elevated levels of specific metabolites, including N,N-dimethylglycine, alanine, and valine, were associated with increased blood pressure, worse obstetric outcomes, and poorer end-organ function, particularly renal and hepatic damage. Metabolomic analysis of PE+ individuals indicates heightened disturbances in nitrogen metabolism, methionine, and urea cycles. Additionally, the exacerbated metabolic disturbance may have disclosed renal impairment and hepatic dysfunction, evidenced by elevated levels of creatine and alanine. These findings not only contribute novel insights but also provide a more comprehensive understanding of the pathophysiological mechanisms at play in cases of PE+. (AU)

• FAPESP's process: 23/08897-1 - Analysis of the circulating metabolomic profile of pregnant women with pre-eclampsia
• Grantee: Julyane Natsumi Saito Kaihara
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 18/24069-3 - ReSEARCH: Recognizing Signatures of the Exposome to Anticipate the Risks for a Continuous Health
• Grantee: Fernando Barbosa Júnior
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/07230-8 - Arginase in preeclampsia: study of genetic polymorphism, circulating factors and in vitro assays
• Grantee: Valeria Cristina Sandrim
• Support Opportunities: Regular Research Grants
• FAPESP's process: 21/12010-7 - Endothelial dysfunction in hypertensive disorders of pregnancy
• Grantee: Valeria Cristina Sandrim
• Support Opportunities: Research Projects - Thematic Grants