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.
- Suneel S Apte
- Suneel S Apte
- Suneel S Apte
- Elliot H Philipson
- Martina Veigl
- David Sedwick
- Sumeda Nandadasa
- Martina Veigl
- Karin Tran-Lundmark
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols: 18-1996 and 18-2045 (Cleveland Clinic IACUC), 2018-11508 (Yale University IACUC) and 43751 (University of Chicago IACUC).
Human subjects: Human umbilical cord samples were collected under an IRB exemption (EX-0118) from Cleveland Clinic for use of discarded tissue without patient identifiers. These cords were used for histological/immunohistologic analysis, in situ hybridization, and transcriptomics of inner vs outer umbilical artery TM. For microarray analysis of umbilical cord artery versus vein, human umbilical cords were collected separately through the National Children's Study under University Hospitals-Case Medical Center approved IRB protocol 01-11-28.
- Karen Downs, University of Wisconsin-Madison School of Medicine and Public Health, United States
- Received: July 2, 2020
- Accepted: September 9, 2020
- Accepted Manuscript published: September 10, 2020 (version 1)
© 2020, Nandadasa et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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