EDN1 and stroke disorder: IR can cause NO reduction and vasoconstrictor endothelin-1 (ET-1) increase involving in the phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signalling pathways, which in turn impairs endothelial cell function and enhances platelet adhesion, activation and aggregation, leading to thrombosis and increased stroke risk (30, 31).