GNAQ p.R183Q endothelial cells fail to align in response to laminar shear stress and exhibit increased expression of MAPK, inflammation, and cell adhesion genes

A key research focus is the influence of shear stress on the development of these malformations, as normal blood flow promotes endothelial stability; consequently, the mutations may disrupt responses to laminar shear stress (LSS), leading to vascular dysfunction and progressive malformation.

In this study, we explore how endothelial cells with the GNAQ p.R183Q somatic mutation found in 90% of syndromic and non-syndromic capillary malformations (CM) respond to increasing levels of LSS. Our findings show that in contrast to control endothelial cells (EC-WT), the mutant endothelial cells (EC-R183Q) fail to align properly under LSS conditions. RNA sequencing revealed altered gene expression in mutant cells exposed to LSS, specifically in pathways related to MAPK, apoptosis, inflammation, and cell adhesion.