Emerging roles of apelin in biology and medicine.
The family of apelin peptides is derived from a single gene and activates the 7-transmembrane G-protein-coupled receptor (GPCR) APJ. Apelins have been shown to be involved in the regulation of cardiovascular function and fluid homeostasis and interestingly represent substrates for ACE2, a carboxypeptidase recently described as a novel key enzyme in the renin-angiotensin-aldosterone system (RAS). APJ has further been reported to be a coreceptor for the infection of CD4-positive cells with HIV in the central nervous system (CNS). Apelin-36 and shorter C-terminal sequences have different potencies and efficacies in regulating these functions. Shorter sequences, especially (Pyr(1))apelin-13, are potent regulators of cardiovascular function, while longer peptides such as apelin-36 are more effective in inhibiting human immunodeficiency virus (HIV) infection by blocking the HIV coreceptor APJ. The pyroglutamate modification characteristic of the short apelin peptide (Pyr(1))apelin-13 indicates paramount biological importance of this peptide. The aim of this review is to compile conclusive evidence for the involvement of apelin/APJ in the regulation of cardiovascular function and HIV pathology, emphasizing the properties of this receptor system that may make it a successful future drug target.
Kleinz
Matthias J
MJ
Clinical Pharmacology Unit, University of Cambridge, Level 6, Centre for Clinical Investigation, Box 110, Addenbrooke's Hospital, Cambridge, CB2 2QQ, UK. mk395@medschl.cam.ac.uk
Davenport
Anthony P
AP
D000818:Animals; D000073861:Apelin; D000075244:Apelin Receptors; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D011485:Protein Binding; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D015728:Receptors, HIV / Q000378:metabolism / Q000502:physiology*
C115436:APLN protein, human; C104575:APLNR protein, human; D000073861:Apelin; D000075244:Apelin Receptors; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D015728:Receptors, HIV