Following the initial stage, the progression of endothelial dysfunction is characterized by the retention of LDL in endothelial cells, leading to its modification to oxidized LDL (ox-LDL) through the activity of enzymes like NADPH oxidases (NOX), lipoxygenases, xanthine oxidase (XO), myeloperoxidase (MPO), mitochondria reactive oxygen species (ROS) and uncoupled endothelial nitric oxide synthase (eNOS) (48, 49). Here, NOS3 is linked to endothelial dysfunction.