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

Research output: Contribution to journalArticle

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 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.

Details

Authors
  • Sumeda Nandadasa
  • Jason M. Szafron
  • Vai Pathak
  • Sae Il Murtada
  • Caroline M. Kraft
  • Anna O’donnell
  • Christian Norvik
  • Clare Hughes
  • Bruce Caterson
  • Miriam S. Domowicz
  • Nancy B. Schwartz
  • Karin Tran-Lundmark
  • Martina Veigl
  • David Sedwick
  • Elliot H. Philipson
  • Jay D. Humphrey
  • Suneel S. Apte
Organisations
External organisations
  • Cleveland Clinic Foundation
  • Yale University
  • Case Western Reserve University
  • University of Chicago
  • Cardiff University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Obstetrics, Gynecology and Reproductive Medicine
Original languageEnglish
Article numbere60683
Number of pages30
JournaleLife
Volume9
Publication statusPublished - 2020
Publication categoryResearch
Peer-reviewedYes