Biological Sciences Division
Published September 10, 2020 | Version v1
Journal article Open

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

Creators

  • 1. Cleveland Clinic Lerner Research Institute
  • 2. Yale University
  • 3. Case Western Reserve University
  • 4. Lund University
  • 5. Cardiff University
  • 6. University of Chicago

Description

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.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

The following data sets were generated:

Nandadasa S Szafron JM Pathak V Murtada S-I Kraft CM O'Donnell A Norvik C Hughes C Caterson B Domowicz MS Schwartz NB Tran-Lundmark K Veigl M Sedwick D Philipson EH Humphrey JD Apte SS (2020) Dryad Digital Repository Human umbilical cord artery inner tunica media vs outer tunica media. https://doi.org/10.5061/dryad.4j0zpc88k

Nandadasa S Szafron JM Pathak V Murtada S-I Kraft CM O'Donnell A Norvik C Hughes C Caterson B Domowicz MS Schwartz NB Tran-Lundmark K Veigl M Sedwick D Philipson EH Humphrey JD Apte SS (2020) Dryad Digital Repository Human umbilical cord artery vs vein. https://doi.org/10.5061/dryad.hdr7sqvfs

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Additional details

Identifiers

DOI
10.7554/eLife.60683
Other
oai:uchicago.tind.io:10008

Related works

Is cited by
https://doi.org/10.7554/eLife.63128 (URL)

Funding

National Institutes of Health
HL107147
National Institutes of Health
HL141130
American Heart Association
17DIA33820024
Sabrina's Foundation
National Children's Study
Formative Research Project
Mark Lauer
Pediatric Research Grant
National Institutes of Health
CA43703
Swedish Heart-Lung Foundation
National Children's Study
HHSN272500800009C

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Pediatrics