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

Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 19, n. 11, p. 22-pg., 2024-11-26.

Resumo

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)

• Processo FAPESP: 23/08897-1 - Análise do perfil metabolômico circulante de gestantes com pré-eclâmpsia
• Beneficiário: Julyane Natsumi Saito Kaihara
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 18/24069-3 - Do biomonitoramento ao reconhecimento de assinaturas do exposoma humano visando antecipar riscos para uma saúde contínua
• Beneficiário: Fernando Barbosa Júnior
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 19/07230-8 - Arginase em pré-eclâmpsia: estudo de polimorfismos genéticos, fatores circulantes e ensaios in vitro
• Beneficiário: Valeria Cristina Sandrim
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 21/12010-7 - Disfunção endotelial em doenças hipertensivas da gestação
• Beneficiário: Valeria Cristina Sandrim
• Modalidade de apoio: Auxílio à Pesquisa - Temático