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

Onderzoeksoutput: Bijdrage aan tijdschriftTijdschriftartikelAcademicpeer review

4 Citaties (Scopus)
37 Downloads (Pure)

Uittreksel

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.

Originele taal-2Engels
Pagina's (van-tot)E3682-E3691
Aantal pagina's10
TijdschriftProceedings of the National Academy of Sciences of the United States of America (PNAS)
Volume115
Nummer van het tijdschrift16
Vroegere onlinedatum2 apr 2018
DOI's
StatusGepubliceerd - 17 apr 2018

Vingerafdruk

Blood Vessels
Homeostasis
Vascular Smooth Muscle
Smooth Muscle Myocytes
Hemodynamics
Mechanics
Morphogenesis
Blood Pressure
Membranes
Genes

Citeer dit

@article{9388417b0e574850b9f6b178edf27fbd,
title = "Mechanosensitivity of Jagged–Notch signaling can induce a switch-type behavior in vascular homeostasis",
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",
author = "Sandra Loerakker and Stassen, {Oscar M.J.A.} and {ter Huurne}, {Fleur M.} and Marcelo Boareto and Bouten, {Carlijn V.C.} and Sahlgren, {Cecilia M.}",
note = "Copyright {\circledC} 2018 the Author(s). Published by PNAS.",
year = "2018",
month = "4",
day = "17",
doi = "10.1073/pnas.1715277115",
language = "English",
volume = "115",
pages = "E3682--E3691",
journal = "Proceedings of the National Academy of Sciences of the United States of America (PNAS)",
issn = "0027-8424",
number = "16",

}

Mechanosensitivity of Jagged–Notch signaling can induce a switch-type behavior in vascular homeostasis. / Loerakker, Sandra; Stassen, Oscar M.J.A.; ter Huurne, Fleur M.; Boareto, Marcelo; Bouten, Carlijn V.C.; Sahlgren, Cecilia M.

In: Proceedings of the National Academy of Sciences of the United States of America (PNAS), Vol. 115, Nr. 16, 17.04.2018, blz. E3682-E3691.

Onderzoeksoutput: Bijdrage aan tijdschriftTijdschriftartikelAcademicpeer review

TY - JOUR

T1 - Mechanosensitivity of Jagged–Notch signaling can induce a switch-type behavior in vascular homeostasis

AU - Loerakker, Sandra

AU - Stassen, Oscar M.J.A.

AU - ter Huurne, Fleur M.

AU - Boareto, Marcelo

AU - Bouten, Carlijn V.C.

AU - Sahlgren, Cecilia M.

N1 - Copyright © 2018 the Author(s). Published by PNAS.

PY - 2018/4/17

Y1 - 2018/4/17

N2 - 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.

AB - 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.

KW - Homeostasis

KW - Jagged

KW - Mechanosensitivity

KW - Notch

UR - http://www.scopus.com/inward/record.url?scp=85045529723&partnerID=8YFLogxK

U2 - 10.1073/pnas.1715277115

DO - 10.1073/pnas.1715277115

M3 - Article

C2 - 29610298

VL - 115

SP - E3682-E3691

JO - Proceedings of the National Academy of Sciences of the United States of America (PNAS)

JF - Proceedings of the National Academy of Sciences of the United States of America (PNAS)

SN - 0027-8424

IS - 16

ER -