Normalization of wall shear stress as a physiological mechanism for regulating maternal uterine artery expansive remodeling during pregnancy

Eliyahu V. Khankin, Nga Ling Ko, Maurizio Mandalà, S. Ananth Karumanchi, George Osol
FASEB BioAdvances2021
Outward remodeling of the maternal uterine circulation during pregnancy is essen- tial for normal uteroplacental perfusion and pregnancy outcome. The physiological mechanism by which this process is regulated is unknown; we hypothesized that it involved the normalization of wall shear stress (WSS). Pregnant Sprague– Dawley rats underwent unilateral ligation of the main uterine artery and vein at the cervical end of the uterus on gestational day 10, thus restricting inflow/outflow of blood into that uterine horn to a single point at the ovarian end; the contralateral sham- operated side provided an internal control. This procedure alters uterine hemodynamics by in- creasing WSS, since the entire uterine horn is supplied by one rather than two vessels. Arterial diameter and blood flow velocity values were measured by intravital ultra- sonographic pulse- wave Doppler on gestational day 20 and used to calculate WSS. Although both ovarian artery lumen diameter and blood velocity increased, WSS was similar in both horns. These data support the concept that increased WSS secondary to hemochorial placentation is the primary physiological stimulus for uterine vascular remodeling and that its normalization may be the primary mechanism that regulates the extent of arterial circumferential growth required to maintain placental perfusion. We further hypothesize that shallow spiral artery invasion, such as occurs in preec- lampsia, limits the increase in upstream shear stress and results in attenuated remod- eling and placental under- perfusion.
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