In addition, it has been reported that increased NO derived from upregulated eNOS may activate PKG signaling as well.47 By comparison, activation of PKA signaling pathway is a direct effect of NPRC deletion and thus, is a major molecular mechanism underling the anti-inflammation and anti-atherosclerosis effect of NPRC deletion in ApoE−/−NPRC−/− mice. This evidence concerns the gene NPR3 and atherosclerosis.