Renal targeted protein therapeutics in experimental overt heart failure with renal dysfunction

Clinical background C-type natriuretic peptide (CNP) is a 22-amino-acid peptide produced mainly in the endothelium and is a ligand for a guanylyl cyclase-coupled receptor, the NPR-B receptor. Recent studies have revealed that in overt heart failure (HF), the predominant natriuretic peptide (NP) receptor in the kidney is the NPR-B receptor. CNP has a potent cardiac unloading action and reduces blood pressure but has minimal renal actions. Based on our previous knowledge, we altered the amino acid (aa) sequence in the ring structure of CNP and fused a 5 aa sequence from ANP to the Nterminus and a 6 aa sequence from BNP to the C-terminus of CNP. We hypothesized that this novel hybrid peptide ABC-NP would maintain CNP's inherent cardiac unloading characteristics plus gaining renal enhancing properties without hypotensive effects.