Mechanosensitivity of Jagged-Notch signaling can induce a switch-type behavior in vascular homeostasis

A1 Journal article (refereed)


Internal Authors/Editors


Publication Details

List of Authors: Sandra Loerakker, Oscar M. J. A. Stassen, Fleur M. ter Huurne, Marcelo Boareto, Carlijn V. C. Bouten, Cecilia M. Sahlgren
Publisher: NATL ACAD SCIENCES
Publication year: 2018
Journal: Proceedings of the National Academy of Sciences
Journal acronym: P NATL ACAD SCI USA
Volume number: 115
Issue number: 16
Start page: E3682
End page: E3691
Number of pages: 10
ISSN: 0027-8424
eISSN: 1091-6490


Abstract

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.


Keywords

homeostasis, Jagged, mechanosensitivity, Notch

Last updated on 2019-22-09 at 05:04