Transcriptional impact of EGFR activation in human female vascular smooth muscle cells

Virginie Dubourg; Gerald Schwerdt; Barbara Schreier; Michael Kopf; Sigrid Mildenberger; Ralf A Benndorf; Michael Gekle

doi:10.1016/j.isci.2023.108286

Transcriptional impact of EGFR activation in human female vascular smooth muscle cells

iScience. 2023 Oct 20;26(11):108286. doi: 10.1016/j.isci.2023.108286. eCollection 2023 Nov 17.

Authors

Virginie Dubourg¹, Gerald Schwerdt¹, Barbara Schreier¹, Michael Kopf¹, Sigrid Mildenberger¹, Ralf A Benndorf², Michael Gekle¹

Affiliations

¹ Julius-Bernstein-Institute of Physiology, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
² Department of Clinical Pharmacy and Pharmacotherapy, Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.

Abstract

Vascular smooth muscle cells (VSMC) are critical for the vascular tone, but they can also drive the development of vascular diseases when they lose their contractile phenotype and de-differentiate. Previous studies showed that the epidermal growth factor receptor (EGFR) of VSMC is critical for vascular health, but most of the underlying mechanisms by which VSMC-EGFR controls vascular fate have remained unknown. We combined RNA-sequencing and bioinformatics analysis to characterize the effect of EGFR-activation on the transcriptome of human primary VSMC (from different female donors) and to identify potentially affected cellular processes. Our results indicate that the activation of human VSMC-EGFR is sufficient to trigger a phenotypical switch toward a proliferative and inflammatory phenotype. The extent of this effect is nonetheless partly donor-dependent. Our hypothesis-generating study thus provides a first insight into mechanisms that could partly explain variable susceptibilities to vascular diseases in between individuals.

Keywords: Cardiovascular medicine; Molecular biology; Transcriptomics.