Differences in placental capillary shear stress in fetal growth restriction may affect endothelial cell function and vascular network formation

Abstract Fetal growth restriction (FGR) affects 5–10% of pregnancies, leading to clinically significant fetal morbidity and mortality. FGR placentae frequently exhibit poor vascular branching, but the mechanisms driving this are poorly understood. We hypothesize that vascular structural malformation...

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Autores principales:	Win M. Tun, Choon Hwai Yap, Shier Nee Saw, Joanna L. James, Alys R. Clark
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7a25616f991b4c4896ea62f5f50b0dca
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spelling	oai:doaj.org-article:7a25616f991b4c4896ea62f5f50b0dca2021-12-02T15:09:28ZDifferences in placental capillary shear stress in fetal growth restriction may affect endothelial cell function and vascular network formation10.1038/s41598-019-46151-62045-2322https://doaj.org/article/7a25616f991b4c4896ea62f5f50b0dca2019-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-46151-6https://doaj.org/toc/2045-2322Abstract Fetal growth restriction (FGR) affects 5–10% of pregnancies, leading to clinically significant fetal morbidity and mortality. FGR placentae frequently exhibit poor vascular branching, but the mechanisms driving this are poorly understood. We hypothesize that vascular structural malformation at the organ level alters microvascular shear stress, impairing angiogenesis. A computational model of placental vasculature predicted elevated placental micro-vascular shear stress in FGR placentae (0.2 Pa in severe FGR vs 0.05 Pa in normal placentae). Endothelial cells cultured under predicted FGR shear stresses migrated significantly slower and with greater persistence than in shear stresses predicted in normal placentae. These cell behaviors suggest a dominance of vessel elongation over branching. Taken together, these results suggest (1) poor vascular development increases vessel shear stress, (2) increased shear stress induces cell behaviors that impair capillary branching angiogenesis, and (3) impaired branching angiogenesis continues to drive elevated shear stress, jeopardizing further vascular formation. Inadequate vascular branching early in gestation could kick off this cyclic loop and continue to negatively impact placental angiogenesis throughout gestation.Win M. TunChoon Hwai YapShier Nee SawJoanna L. JamesAlys R. ClarkNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-10 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Win M. Tun Choon Hwai Yap Shier Nee Saw Joanna L. James Alys R. Clark Differences in placental capillary shear stress in fetal growth restriction may affect endothelial cell function and vascular network formation
description	Abstract Fetal growth restriction (FGR) affects 5–10% of pregnancies, leading to clinically significant fetal morbidity and mortality. FGR placentae frequently exhibit poor vascular branching, but the mechanisms driving this are poorly understood. We hypothesize that vascular structural malformation at the organ level alters microvascular shear stress, impairing angiogenesis. A computational model of placental vasculature predicted elevated placental micro-vascular shear stress in FGR placentae (0.2 Pa in severe FGR vs 0.05 Pa in normal placentae). Endothelial cells cultured under predicted FGR shear stresses migrated significantly slower and with greater persistence than in shear stresses predicted in normal placentae. These cell behaviors suggest a dominance of vessel elongation over branching. Taken together, these results suggest (1) poor vascular development increases vessel shear stress, (2) increased shear stress induces cell behaviors that impair capillary branching angiogenesis, and (3) impaired branching angiogenesis continues to drive elevated shear stress, jeopardizing further vascular formation. Inadequate vascular branching early in gestation could kick off this cyclic loop and continue to negatively impact placental angiogenesis throughout gestation.
format	article
author	Win M. Tun Choon Hwai Yap Shier Nee Saw Joanna L. James Alys R. Clark
author_facet	Win M. Tun Choon Hwai Yap Shier Nee Saw Joanna L. James Alys R. Clark
author_sort	Win M. Tun
title	Differences in placental capillary shear stress in fetal growth restriction may affect endothelial cell function and vascular network formation
title_short	Differences in placental capillary shear stress in fetal growth restriction may affect endothelial cell function and vascular network formation
title_full	Differences in placental capillary shear stress in fetal growth restriction may affect endothelial cell function and vascular network formation
title_fullStr	Differences in placental capillary shear stress in fetal growth restriction may affect endothelial cell function and vascular network formation
title_full_unstemmed	Differences in placental capillary shear stress in fetal growth restriction may affect endothelial cell function and vascular network formation
title_sort	differences in placental capillary shear stress in fetal growth restriction may affect endothelial cell function and vascular network formation
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/7a25616f991b4c4896ea62f5f50b0dca
work_keys_str_mv	AT winmtun differencesinplacentalcapillaryshearstressinfetalgrowthrestrictionmayaffectendothelialcellfunctionandvascularnetworkformation AT choonhwaiyap differencesinplacentalcapillaryshearstressinfetalgrowthrestrictionmayaffectendothelialcellfunctionandvascularnetworkformation AT shierneesaw differencesinplacentalcapillaryshearstressinfetalgrowthrestrictionmayaffectendothelialcellfunctionandvascularnetworkformation AT joannaljames differencesinplacentalcapillaryshearstressinfetalgrowthrestrictionmayaffectendothelialcellfunctionandvascularnetworkformation AT alysrclark differencesinplacentalcapillaryshearstressinfetalgrowthrestrictionmayaffectendothelialcellfunctionandvascularnetworkformation
_version_	1718387822965030912

Differences in placental capillary shear stress in fetal growth restriction may affect endothelial cell function and vascular network formation

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