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Vascular dimorphism ensured by regulated proteoglycan dynamics favors rapid umbilical artery closure at birth

Nandadasa, Sumeda ; Szafron, Jason M. ; Pathak, Vai ; Murtada, Sae Il ; Kraft, Caroline M. ; O’donnell, Anna ; Norvik, Christian LU ; Hughes, Clare ; Caterson, Bruce and Domowicz, Miriam S. , et al. (2020) In eLife 9.
Abstract

The umbilical artery lumen closes rapidly at birth, preventing neonatal blood loss, whereas the umbilical vein remains patent longer. Here, analysis of umbilical cords from humans and other mammals identified differential arterial-venous proteoglycan dynamics as a determinant of these contrasting vascular responses. The umbilical artery, but not the vein, has an inner layer enriched in the hydrated proteoglycan aggrecan, external to which lie contraction-primed smooth muscle cells (SMC). At birth, SMC contraction drives inner layer buckling and centripetal displacement to occlude the arterial lumen, a mechanism revealed by biomechanical observations and confirmed by computational analyses. This vascular dimorphism arises from spatially... (More)

The umbilical artery lumen closes rapidly at birth, preventing neonatal blood loss, whereas the umbilical vein remains patent longer. Here, analysis of umbilical cords from humans and other mammals identified differential arterial-venous proteoglycan dynamics as a determinant of these contrasting vascular responses. The umbilical artery, but not the vein, has an inner layer enriched in the hydrated proteoglycan aggrecan, external to which lie contraction-primed smooth muscle cells (SMC). At birth, SMC contraction drives inner layer buckling and centripetal displacement to occlude the arterial lumen, a mechanism revealed by biomechanical observations and confirmed by computational analyses. This vascular dimorphism arises from spatially regulated proteoglycan expression and breakdown. Mice lacking aggrecan or the metalloprotease ADAMTS1, which degrades proteoglycans, demonstrate their opposing roles in umbilical vascular dimorphism, including effects on SMC differentiation. Umbilical vessel dimorphism is conserved in mammals, suggesting that differential proteoglycan dynamics and inner layer buckling were positively selected during evolution.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
eLife
volume
9
article number
e60683
pages
30 pages
publisher
eLife Sciences Publications
external identifiers
  • scopus:85092065002
  • pmid:32909945
ISSN
2050-084X
DOI
10.7554/ELIFE.60683
language
English
LU publication?
yes
id
758dd1ac-1663-483f-b462-3d033261d271
date added to LUP
2020-11-03 12:44:20
date last changed
2024-06-14 01:27:21
@article{758dd1ac-1663-483f-b462-3d033261d271,
  abstract     = {{<p>The umbilical artery lumen closes rapidly at birth, preventing neonatal blood loss, whereas the umbilical vein remains patent longer. Here, analysis of umbilical cords from humans and other mammals identified differential arterial-venous proteoglycan dynamics as a determinant of these contrasting vascular responses. The umbilical artery, but not the vein, has an inner layer enriched in the hydrated proteoglycan aggrecan, external to which lie contraction-primed smooth muscle cells (SMC). At birth, SMC contraction drives inner layer buckling and centripetal displacement to occlude the arterial lumen, a mechanism revealed by biomechanical observations and confirmed by computational analyses. This vascular dimorphism arises from spatially regulated proteoglycan expression and breakdown. Mice lacking aggrecan or the metalloprotease ADAMTS1, which degrades proteoglycans, demonstrate their opposing roles in umbilical vascular dimorphism, including effects on SMC differentiation. Umbilical vessel dimorphism is conserved in mammals, suggesting that differential proteoglycan dynamics and inner layer buckling were positively selected during evolution.</p>}},
  author       = {{Nandadasa, Sumeda and Szafron, Jason M. and Pathak, Vai and Murtada, Sae Il and Kraft, Caroline M. and O’donnell, Anna and Norvik, Christian and Hughes, Clare and Caterson, Bruce and Domowicz, Miriam S. and Schwartz, Nancy B. and Tran-Lundmark, Karin and Veigl, Martina and Sedwick, David and Philipson, Elliot H. and Humphrey, Jay D. and Apte, Suneel S.}},
  issn         = {{2050-084X}},
  language     = {{eng}},
  publisher    = {{eLife Sciences Publications}},
  series       = {{eLife}},
  title        = {{Vascular dimorphism ensured by regulated proteoglycan dynamics favors rapid umbilical artery closure at birth}},
  url          = {{http://dx.doi.org/10.7554/ELIFE.60683}},
  doi          = {{10.7554/ELIFE.60683}},
  volume       = {{9}},
  year         = {{2020}},
}