Apelin and its Receptor: An Overview

Apelin protein is an endogenous ligand of Apelin Receptor (APJ). APJ is a member of G-protein coupled receptor family. Both apelin and its receptor express extensively in the human body. Apelin receptor activation occurs by its cognate peptide ligand, apelin and many physiological effects, including vasodilation, vasoconstriction, angiogenesis, fluid homeostasis, neuroendocrine response to stress and energy metabolism. Apelin derived from its precursor might yield a number of bioactive peptides. Apelin is synthesised as an immature single peptide (preproapelin) which consists of 77 amino acids. In the endoplasmic reticulum, preproapelin is cleaved by endopeptidases to a 55 amino acid proapelin and subsequently, to various biologically active apelin-36, apelin-17 and apelin-13 isoforms. Post-translation, the apelin containing the pyroglutamate group at N-terminus of the peptide is modified to pyroglutamate apelin 13. In adipocytes, proprotein convertase subtilisin/kexin 3 directly cleaves the proapelin to apelin 13 and does not produce any longer isoforms. In contrast, Angiotensin Converting Enzyme 2- (ACE-2) cleaves at proline-phenylalanine site at C-terminus and renders apelin 13 and apelin 36 inactive. To date, ACE-2 is the only known enzyme for apelin degradation. The C-terminal region is responsible for receptor binding and subsequent activation. Prior research suggests the role of apelin and its receptor in pathogenesis of various conditions including preeclampsia, hypertension, cardiovascular diseases, diabetes mellitus, obesity and cancer. Despite its established importance and link to therapeutic target, the precise role of this apelin/APJ remain obscure. In this attempt, we summarised the structure, chemistry, biosynthesis, expression and gene regulation, distribution, receptor binding mechanism, biological functions and therapeutic applications along with the associated recent advances.