As endothelial dysfunction is considered an early causative event in the development of atherosclerosis (Davignon and Ganz, 2004), we sought to determine whether enhancement of endothelial KCa2.3/KCa3.1 channel activity in vivo would ameliorate endothelial dysfunction in the aorta of atherosclerotic Apoe−/− mice maintained on a high fat diet (HFD). This evidence concerns the gene KCNN4 and endothelial dysfunction.