Fluid shear stress regulates vascular remodeling via VEGFR-3 activation, although independently of its ligand, VEGF-C, in the uterus during pregnancy

Park,Yang-Gyu; Choi,Jawun; Jung,Hye-Kang; Song,In  Kyu; Shin,Yongwhan; Park,Sang-Youel; Seol,Jae-Won

doi:10.3892/ijmm.2017.3108

Fluid shear stress regulates vascular remodeling via VEGFR-3 activation, although independently of its ligand, VEGF-C, in the uterus during pregnancy

Authors:
- Yang-Gyu Park
- Jawun Choi
- Hye-Kang Jung
- In Kyu Song
- Yongwhan Shin
- Sang-Youel Park
- Jae-Won Seol
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Affiliations: Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Iksan, Jwonbuk 54596, Republic of Korea, Auckland International College, Auckland 0600, New Zealand
Published online on: August 25, 2017 https://doi.org/10.3892/ijmm.2017.3108
Pages: 1210-1216
Copyright: © Park et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Early pregnancy is characterized by an increase in the blood volume of the uterus for embryonic development, thereby exerting fluid shear stress (FSS) on the vascular walls. The uterus experiences vascular remodeling to accommodate the increased blood flow. The blood flow‑induced FSS elevates the expression of vascular endothelial growth factors (VEGFs) and their receptors, and regulates vascular remodeling through the activation of VEGF receptor-3 (VEGFR-3). However, the mechanisms responsible for FSS-induced VEGFR-3 expression in the uterus during pregnancy are unclear. In this study, we demonstrate that vascular remodeling in the uterus during pregnancy is regulated by FSS-induced VEGFR-3 expression. We examined the association between VEGFR-3 and FSS through in vivo and in vitro experiments. In vivo experiments revealed VEGFR-3 expression in the CD31-positive region of the uterus of pregnant mice; VEGF-C (ligand for VEGFR‑3) was undetected in the uterus. These results confirmed that VEGFR-3 expression in the endometrium is independent of its ligand. In vitro studies experiments revealed that FSS induced morphological changes and increased VEGFR-3 expression in human uterine microvascular endothelial cells. Thus, VEGFR-3 activation by FSS is associated with vascular remodeling to allow increased blood flow in the uterus during pregnancy.

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