Burnett, John

Although CNP (C‐type natriuretic peptide) was first identified in brain tissue, its systemic expression and release is mainly located to the endothelial lining of the vasculature. As such, CNP should not be viewed as a classic blood‐borne hormone but rather as a local factor that supports the integrity of vascular function. Albeit CNP is structurally related to both ANP and BNP (A‐ and B‐type natriuretic peptide), the main signaling pathway is through a specific membrane‐bound receptor without crosstalk from endocrine ANP and BNP. CNP expression and CNP‐mediated effects can thus be uniquely targeted without interference from the related cardiac NPs. In this perspective, we present the CNP system as a largely overlooked target for potential intervention in cardiometabolic disease, hypertension, and diabetes before onset of complications and overt heart failure. To fully unleash this potential, with this perspective, we hope to fuel renewed interest with a focus on use of human in vitro and ex vivo systems as well as experimental medical approaches and human cohort data.