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

Vascular malformations are caused by germline or somatic mutations. A key research focus is the influence of laminar shear stress (LSS) on the development of these malformations. In this study, we explore how endothelial cells (EC) with the GNAQ p.R183Q somatic mutation, which is 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 EC (EC-WT), the mutant EC (EC-R183Q) fail to align under LSS conditions. RNA sequencing revealed altered gene expression in EC-R183Q exposed to LSS, specifically in pathways related to MAPK, apoptosis, inflammation, and cell adhesion. These results suggest impaired mechanosensory responses in GNAQ p.R183Q endothelium that may contribute to vascular dysfunction in CM.