Maternal heart exhibits metabolic and redox adaptations post-uncomplicated pregnancy

Biochim Biophys Acta Mol Basis Dis. 2025 Jan;1871(1):167539. doi: 10.1016/j.bbadis.2024.167539. Epub 2024 Oct 6.

Abstract

Pregnancy may be a challenging period for the maternal systems and has been regarded as a stress test, as imperceptible/mild dysfunctions eventually present may be exacerbated during this period. The cardiovascular system is no exception, and several morphological and functional adaptations accompanying pregnancy have been described. However, long-term pregnancy-induced cardiac molecular alterations remain highly unexplored. The postpartum is marked by reverse remodeling of the pregnancy-induced cardiovascular adaptations, representing a possible critical period for assessing future maternal cardiovascular health. The current study explored the molecular and metabolic alterations in the cardiac tissue eight weeks after a physiological uncomplicated pregnancy. Female Sprague-Dawley rats were fed a chow diet through pregnancy, lactation, and weaning and compared to their non-pregnant counterparts. Eight weeks postpartum, increased levels of the phosphorylated form of AMPKα (Thr172) and its ratio to total AMPKα indicated possible alterations in cardiac metabolic flexibility, accompanied by increased Pparα and Hif1α transcripts levels. Additionally, postpartum hearts exhibited higher mitochondrial ATP and NADH levels without major changes in mitochondrial respiratory function. Elevated Nrf2 levels in the cardiac tissue suggested potential implications for cardiac redox balance, further supported by increased levels or activity of proteins directly regulated by Nrf2. The findings herein reported suggest that at eight weeks postpartum, molecular alterations induced by pregnancy, especially regarding redox balance, are still observed in the mothers' heart. These alterations present at late postpartum may open new avenues to understand the different risk for cardiovascular complications development after normal pregnancies.

Keywords: Cardiac health post-pregnancy; Cardiac metabolic flexibility; Cardiac redox balance postpartum; Maternal cardiovascular health; Postpartum cardiac remodeling; Pregnancy-induced heart molecular adaptations.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Adaptation, Physiological*
  • Animals
  • Female
  • Heart
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Lactation / metabolism
  • Myocardium* / metabolism
  • NF-E2-Related Factor 2* / genetics
  • NF-E2-Related Factor 2* / metabolism
  • Oxidation-Reduction*
  • PPAR alpha* / genetics
  • PPAR alpha* / metabolism
  • Postpartum Period / metabolism
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley*

Substances

  • AMP-Activated Protein Kinases
  • Hif1a protein, rat
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • PPAR alpha