A1 Refereed original research article in a scientific journal
Mechanosensitivity of Jagged-Notch signaling can induce a switch-type behavior in vascular homeostasis
Authors: Loerakker Sandra, Stassen Oscar MJA, ter Huurne Fleur M, Boareto Marcelo, Bouten Carlijn VC, Sahlgren Cecilia M
Publisher: NATL ACAD SCIENCES
Publication year: 2018
Journal: Proceedings of the National Academy of Sciences of the United States of America
Journal name in source: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Journal acronym: P NATL ACAD SCI USA
Volume: 115
Issue: 16
First page : E3682
Last page: E3691
Number of pages: 10
ISSN: 0027-8424
eISSN: 1091-6490
DOI: https://doi.org/10.1073/pnas.1715277115
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/30898984
Hemodynamic forces and Notch signaling are both known as key regulators of arterial remodeling and homeostasis. However, how these two factors integrate in vascular morphogenesis and homeostasis is unclear. Here, we combined experiments and modeling to evaluate the impact of the integration of mechanics and Notch signaling on vascular homeostasis. Vascular smooth muscle cells (VSMCs) were cyclically stretched on flexible membranes, as quantified via video tracking, demonstrating that the expression of Jagged1, Notch3, and target genes was down-regulated with strain. The data were incorporated in a computational framework of Notch signaling in the vascular wall, where the mechanical load was defined by the vascular geometry and blood pressure. Upon increasing wall thickness, the model predicted a switch-type behavior of the Notch signaling state with a steep transition of synthetic toward contractile VSMCs at a certain transition thickness. These thicknesses varied per investigated arterial location and were in good agreement with human anatomical data, thereby suggesting that the Notch response to hemodynamics plays an important role in the establishment of vascular homeostasis.
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