Nirupama Ramadas, Kailyn Lowder, Joshua Dutton, Fatima Trebak, Camille Faes, John H Griffin, Rafal Pawlinski, Laurent O Mosnier, Erica M Sparkenbaugh
Sickle cell disease (SCD) is a hereditary hemoglobinopathy marked by hemolytic anemia and vaso-occlusive events (VOE). Chronic endothelial activation, inflammation, and coagulation activation contribute to vascular congestion, VOE, and end-organ damage. Coagulation proteases like thrombin and activated protein C (APC) modulate inflammation and endothelial dysfunction by activating protease-activated receptor 1 (PAR1), a G-protein coupled receptor. Thrombin cleaves PAR1 at Arg41, while APC cleaves PAR1 at Arg46, initiating either pro-inflammatory or cytoprotective signaling, respectively, a signaling conundrum known as biased agonism...
April 19, 2024: Blood Advances