Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Allerkamp, HH; Leighton, SC; Pole, T; Clark, AR; James, JL.
Synergistic regulation of uterine radial artery adaptation to pregnancy by paracrine and haemodynamic factors.
Am J Physiol Heart Circ Physiol. 2023;
Doi: 10.1152/ajpheart.00205.2023
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- Allerkamp Hanna
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- Abstract:
- Fetal growth throughout pregnancy relies on delivery of an increasing volume of maternal blood to the placenta. To facilitate this, the uterine vascular network adapts structurally and functionally, resulting in wider blood vessels with decreased flow-mediated reactivity. Impaired remodeling of the rate-limiting uterine radial arteries has been associated with fetal growth restriction. However, the mechanisms underlying normal or pathological radial artery remodeling are poorly understood. Here, we used pressure myography to determine the roles of haemodynamic (resistance, flow rate, shear stress) and paracrine (β-estradiol, progesterone, placental growth factor (PlGF), vascular endothelial growth factor) factors on rat radial artery reactivity. We show that β-estradiol, progesterone, and PlGF attenuate flow-mediated constriction of radial arteries from non-pregnant rats, allowing them to withstand higher flow rates in a similar manner to pregnant vessels. This effect was partly mediated by nitric oxide (NO) production. To better understand how the combination of paracrine factors and shear stress may impact human radial artery remodeling in the first half of gestation, computational models of uterine haemodynamics, incorporating physiological parameters for trophoblast plugging and spiral artery remodeling, were used to predict shear stress in the upstream radial arteries across the first half of pregnancy. Human microvascular endothelial cells subjected to these predicted shear stresses demonstrated higher NO production when paracrine factors were added. This suggests that synergistic effects of paracrine and haemodynamic factors induce uterine vascular remodeling, and that alterations in this balance could impair radial artery adaptation, limiting blood flow to the placenta and negatively impacting fetal growth.
- Find related publications in this database (Keywords)
- computational model
- pregnancy
- shear stress
- uterine radial arteries
- vascular adaptation