title: Immunocytochemical localisation of the apelin receptor, APJ, to human cardiomyocytes, vascular smooth muscle and endothelial cells.
abstract: The novel G protein-coupled receptor APJ, recently paired with the proposed cognate peptide ligand apelin, mediates potent vasodilator and positive inotropic actions in rats. Radioligand binding showed apelin receptors in rat and human heart and human large conduit vessels. The specific cell types expressing the receptor, however, have not been determined. Apelin, the cognate receptor ligand, is present in endothelial cells. However, the exact pathway of endothelial apelin synthesis and secretion is not known. We therefore investigated the cellular distribution of APJ receptor-like immunoreactivity (APJ-LI) in a range of human tissues using immunocytochemistry and fluorescent double staining confocal microscopy. The same techniques were applied to determine the intracellular localisation of apelin-like immunoreactivity (apelin-LI) in cultured human umbilical vein endothelial cells (HUVECs). APJ-LI is present in endothelial cells, vascular smooth muscle cells and cardiomyocytes. Apelin-LI localises to secretory vesicles and the Golgi complex/endoplasmic reticulum of HUVECs. Apelin-LI does not co-localise with von Willebrand factor in Weibel-Palade bodies, suggesting synthesis of apelin via the constitutive pathway. The proximity of receptor and ligand in the human vasculature, together with evidence for local vascular apelin synthesis, suggests an important role for APJ/apelin as a paracrine cardiovascular regulator system.
authors.affiliation: 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
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Kleinz
authors.forename: Jeremy N
authors.initials: JN
authors.lastname: Skepper
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Davenport
mesh_terms: D000818:Animals; D000073861:Apelin; D000075244:Apelin Receptors; D002352:Carrier Proteins / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism* / Q000648:ultrastructure; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D008856:Microscopy, Fluorescence / Q000379:methods; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D022142:Secretory Vesicles / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology
chemical_list: C115436:APLN protein, human; C104575:APLNR protein, human; D000073861:Apelin; D000075244:Apelin Receptors; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled