Although earlier studies showed that increased NPRC expression was associated with instability of atherosclerotic plaques,20,21 a recent study found that CNP plays a major role in maintaining vascular homeostasis in atherosclerosis.22 More recently, binding of CNP with NPRC has been found to promote angiogenesis and vascular remodeling in response to ischemia via activating Gi, ERK1/2, and phosphoinositide 3-kinase γ/AKT signaling pathways.23 Thus, it remains elusive whether NPRC exerts a beneficial or harmful effect on AS lesions and what mechanism is involved in these effects. This evidence concerns the gene CNP and atherosclerosis.