Unlocking the Therapeutic Potential of Apelin
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See related article, pp 365–377
Apelin was identified in 1998 as the endogenous ligand for the then orphan G-protein–coupled receptor, APJ, now renamed the apelin receptor. Widely expressed in the central nervous system and peripheral tissues, the apelin system participates in a diverse array of processes, including glucose metabolism, immune function, and fluid homeostasis.1 However, its principal physiological role seems to be related to its cardiovascular actions.
Apelin is synthesized as a 77-amino acid prepropeptide that is cleaved into a mature 36-amino acid peptide. Shorter more active isoforms have also been identified, with the pyroglutamated 13-amino acid apelin, (Pyr1)apelin-13, being the most potent and abundant form in cardiac tissue.2 The main source of plasma apelin is unclear although the vascular endothelium and the atria of the heart are likely to be significant contributors. Apelin has a brief plasma half-life of <5 minutes in humans, and its cardiovascular effects are relatively short lived.3,4 One enzyme that has long been implicated in the inactivation of apelin peptides is angiotensin-converting enzyme (ACE) type 2, a carboxypeptidase that negatively regulates the renin–angiotensin–aldosterone system by cleaving angiotensin II to the biologically inactive peptide angiotensin 1–9 or angiotensin 1–7. Although ACE2 was previously reported to hydrolyse both apelin-13 and apelin-36 with high catalytic efficiency,5 its ability to inactivate these peptides and physiological significance was hitherto unclear (Figure).
In this issue of Hypertension, Wang et al6 present a comprehensive series of studies that confirm an important role for ACE2 in …