Endotheliaal LRRC8C reguleert vasculaire reactiviteit en bloeddruk

BACKGROUND:Endothelial mechanosensing is essential for controlling vascular tone. LRRC8A (leucine-rich repeat-containing protein 8A) was previously identified as a core subunit of the mechanoresponsive LRRC8 complex, functionally encoding the endothelial volume regulatory anion channel and regulating vascular function. This study aims to identify the molecular identity of the endothelial LRRC8 complex and its function in vascular reactivity and blood pressure control.METHODS:We generated germline epitope-taggedLrrc8a-3xFlag knock-in mice and endothelium-specificLrrc8a-3xFlag overexpression mice to permit LRRC8A and LRRC8C immunoprecipitation and define LRRC8 subunit interactions. We combined in vivo and in vitro loss-of-function models, electrophysiology, immunoblotting, and pressure myography of third-order mesenteric arteries to examine the contributions of individual LRRC8A/B/C subunits to vascular function and underlying signaling pathways. The contributions of LRRC8C to blood pres