Although opposing views exist [41], this evidence deriving from two genetically targeted mouse models lacking either the α1 subunit of the NO-GC heterodimer or cGKI strongly support a pro-atherogenic role for the endogenous NO-GC/cGMP/cGKI pathway, which is consistent with our present report on the pathophysiological functions of CRP4 in VSMC plasticity and atherosclerosis development. This evidence concerns the gene PRKG1 and atherosclerosis.