Furthermore, regular consumption of pomegranate juice has been shown to reduce atherogenic LDL alterations in Apo E deficient animals [145], and to prevent endothelial dysfunction due to the activation of the serine/threonine-protein kinase/Endothelial nitric oxide synthase (Akt/eNOS) pathway, possibly mediated by HDL through its molecular component sphingosine-1 phosphate [146]. Here, NOS3 is linked to endothelial dysfunction.