Pro-atrial natriuretic peptide (pro-ANP)

Pro-atrial natriuretic peptide (pro-ANP) is the 126-amino acid precursor to the active hormone atrial natriuretic peptide (ANP), which is primarily synthesized and stored in cardiac myocytes (UniProt P01160). The Arg-98–centered cleavage motif, specifically the peptide bond between Arginine-98 and Serine-99, serves as the critical site for proteolytic processing by the transmembrane serine protease Corin (Yan et al., 2000). Upon cardiac wall stretch or volume overload, Corin cleaves pro-ANP at this motif to release the biologically active 28-amino acid C-terminal ANP and an N-terminal fragment (NT-proANP) (Potter et al., 2006). Active ANP then binds to the natriuretic peptide receptor A (NPR-A), triggering the production of cyclic GMP to induce vasodilation, natriuresis, and diuresis, thereby regulating blood pressure and fluid volume (Potter et al., 2006). In clinical conditions like heart failure, the processing of pro-ANP at this Arg-98 site is often impaired, leading to high levels of the inactive precursor and insufficient active hormone, a phenomenon known as the 'ANP paradox' (Ichiki et al., 2011). Consequently, this cleavage motif is a focal point for therapeutic strategies aimed at restoring ANP activity, either through the administration of recombinant ANP analogs like carperitide or by inhibiting the degradation of the active peptide using neprilysin inhibitors such as sacubitril (Ichiki et al., 2011). Understanding the structural integrity and processing efficiency of this motif is also vital for the development of diagnostic biomarkers like MR-proANP, which reflect cardiac stress and disease progression.

Other names

NPPAAtrial natriuretic factorANFPrepro-ANPCardionatrinCDD-ANF

Activation of natriuretic peptide receptor A (NPR-A) via the released active ANP peptide; inhibition of neprilysin to prevent degradation of the active peptide; proteolytic cleavage of the pro-peptide precursor by Corin.