Insulin resistance, in turn, is a known risk factor for atherosclerosis: it impairs the phosphatidylinositol 3-kinase–nitric oxide pathway in endothelial cells, activates the mitogen-activated protein kinase pathway (promoting vasoconstriction), and directly stimulates vascular smooth muscle cells to induce vasoconstriction independently of endothelial cells (23). This evidence concerns the gene WNK2 and Insulin resistance.