Impairment of the extrusion transporter for asymmetric dimethyl-l-arginine: A novel mechanism underlying vasospastic angina

► We propose a novel mechanism underlying human endothelial and platelet dysfunction. ► We show endothelial ADMA overload due to lack of the extrusion transporter y+LAT. ► ADMA overload leads to endothelial NO synthase dysfunction and oxidative stress. ► Oral l-arginine therapy normalizes endothelial ADMA levels via clearance by CAT-1. ► The present findings contribute to the understanding of the l-arginine paradox.