Vascular Dynamics of Pregnancy-Associated Peptides

During gestation, the maternal cardiovascular system undergoes profound remodelling to accommodate the increasing demands of the developing foetus. Central to this adaptation is a finely tuned network of vasoactive peptides that regulate uteroplacental blood flow, vascular tone and endothelial function. Among these, adrenomedullin and its paralogue intermedin (also known as adrenomedullin 2) facilitate vasodilatation, promote angiogenesis and modulate vascular permeability within the placenta. Calcitonin gene-related peptide (CGRP) further supports this milieu by counteracting vasoconstrictor stimuli and preserving endothelial bioenergetics. These peptides exert their effects via G protein-coupled receptor complexes comprising the calcitonin receptor-like receptor (CRLR) and receptor activity-modifying proteins, ensuring tissue-specific responses. Dysregulation of this system, whether through hypoxia-driven alterations in peptide expression or imbalance between vasodilators and vasoconstrictors, underpins disorders such as preeclampsia and foetal growth restriction. The global significance of understanding these dynamics lies in the potential to refine biomarkers for early detection of vascular complications in pregnancy and to develop targeted therapies that can restore vascular homeostasis without compromising maternal or foetal safety.

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Vascular Dynamics of Pregnancy-Associated Peptides publication trend

The graph below shows the total number of articles in vascular dynamics of pregnancy-associated peptides across all publications each year (not limited to Nature Index journals).

Technical terms

Adrenomedullin (ADM): A vasodilatory peptide that promotes angiogenesis and vascular permeability in the placenta.

Intermedin (ADM2): A paralogue of adrenomedullin sharing receptors but with distinct roles in vascular and metabolic adaptation.

Calcitonin gene-related peptide (CGRP): A potent vasodilator that counteracts vasoconstriction and supports endothelial bioenergetics.

Soluble fms-like tyrosine kinase-1 (sFLT-1): An anti-angiogenic factor implicated in preeclampsia that disrupts vascular homeostasis.

Trophoblast: Placental cells that invade maternal tissue to establish blood flow to the developing foetus.

Hypoxia-inducible factor-1α (HIF-1α): A transcription factor activated under low oxygen that regulates expression of vasoactive peptides.

References

1. Altered expression of ADM and ADM2 by hypoxia regulates migration of trophoblast and HLA-G expression. Biology of Reproduction (2020).
2. Role of adrenomedullin2/ intermedin in pregnancy induced vascular and metabolic adaptation in mice. Frontiers in Physiology (2023).
3. Calcitonin gene-related peptide protects from soluble fms-like tyrosine kinase-1-induced vascular dysfunction in a preeclampsia mouse model. Frontiers in Physiology (2023).