Platelet CFTR inhibition enhances arterial thrombosis via increasing intracellular Cl^- concentration and activation of SGK1 signaling pathway.

ABSTRACT: Platelet hyperactivity is essential for thrombus formation in coronary artery diseases (CAD). Dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) in patients with cystic fibrosis elevates intracellular Cl^- levels ([Cl^-]_i) and enhanced platelet hyperactivity. In this study, we explored whether alteration of [Cl^-]_i has a pathological role in regulating platelet hyperactivity and arterial thrombosis formation. CFTR expression was significantly decreased, while [Cl^-]_i was increased in platelets from CAD patients. In a FeCl₃-induced mouse mesenteric arteriole thrombosis model, platelet-specific Cftr-knockout and/or pre-administration of ion channel inhibitor CFTRinh-172 increased pl

SUBMITTER: Yang HY 

PROVIDER: S-EPMC9525590 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature