Notch signaling regulates strain-mediated phenotypic switching of vascular smooth muscle cells

Cansu Karakaya; Mark C van Turnhout; Valery L Visser; Tommaso Ristori; Carlijn V C Bouten; Cecilia M Sahlgren; Sandra Loerakker

doi:10.3389/fcell.2022.910503

Notch signaling regulates strain-mediated phenotypic switching of vascular smooth muscle cells

Front Cell Dev Biol. 2022 Aug 12:10:910503. doi: 10.3389/fcell.2022.910503. eCollection 2022.

Authors

Cansu Karakaya^{1

2}, Mark C van Turnhout¹, Valery L Visser¹, Tommaso Ristori^{1

2}, Carlijn V C Bouten^{1

2}, Cecilia M Sahlgren^{1

2

3}, Sandra Loerakker^{1

2}

Affiliations

¹ Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands.
² Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, Netherlands.
³ Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland.

Abstract

Mechanical stimuli experienced by vascular smooth muscle cells (VSMCs) and mechanosensitive Notch signaling are important regulators of vascular growth and remodeling. However, the interplay between mechanical cues and Notch signaling, and its contribution to regulate the VSMC phenotype are still unclear. Here, we investigated the role of Notch signaling in regulating strain-mediated changes in VSMC phenotype. Synthetic and contractile VSMCs were cyclically stretched for 48 h to determine the temporal changes in phenotypic features. Different magnitudes of strain were applied to investigate its effect on Notch mechanosensitivity and the phenotypic regulation of VSMCs. In addition, Notch signaling was inhibited via DAPT treatment and activated with immobilized Jagged1 ligands to understand the role of Notch on strain-mediated phenotypic changes of VSMCs. Our data demonstrate that cyclic strain induces a decrease in Notch signaling along with a loss of VSMC contractile features. Accordingly, the activation of Notch signaling during cyclic stretching partially rescued the contractile features of VSMCs. These findings demonstrate that Notch signaling has an important role in regulating strain-mediated phenotypic switching of VSMCs.

Keywords: Notch signaling; cardiovascular; mechanosensitive; phenotype; strain; stretch quantification; vascular smooth muscle cells.