Immunocytochemical localization of the endogenous vasoactive peptide apelin to human vascular and endocardial endothelial cells.
Apelin, the proposed endogenous peptide ligand of the novel G-protein-coupled receptor APJ, has been shown to possess potent vasodilator and positive inotropic effects in rats and humans in vivo. However, in humans, no endogenous source of apelin has been reported. Therefore, based on the presence of APJ and mRNA encoding apelin in human tissues, we investigated the expression of apelin in fresh-frozen human tissue from right atrium, left ventricle, lung, kidney, adrenal and large conduit vessels using immunocytochemistry. Apelin-like immunoreactivity (apelin-LI) was detected in vascular endothelial cells lining blood vessels in the human heart, kidney, adrenal gland and lung and in endothelial cells of large conduit vessels. Apelin-LI was also present in endocardial endothelial cells lining recesses of the right atrium. Apelin-LI was not present or below the level of detection in cardiomyocytes, Purkinje's cells, pulmonary or renal epithelial cells, secretory cells of the adrenal gland, vascular smooth muscle cells, adipocytes, nerves and connective tissue. The restricted presence of apelin-LI in endothelial cells suggests that endothelial apelin may play a role as a locally secreted cardiovascular mediator acting on APJ receptors present on the vascular smooth muscle and on cardiac myocytes to regulate vascular tone and cardiac contractility.
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
Matthias J
MJ
Kleinz
Anthony P
AP
Davenport
D000311:Adrenal Glands / Q000737:chemistry / Q000166:cytology; D000906:Antibodies / Q000276:immunology; D000073861:Apelin; D000075244:Apelin Receptors; D002352:Carrier Proteins / Q000032:analysis* / Q000276:immunology / Q000502:physiology; D003331:Coronary Vessels / Q000737:chemistry / Q000166:cytology; D003429:Cross Reactions / Q000276:immunology; D004699:Endocardium / Q000737:chemistry* / Q000166:cytology; D042783:Endothelial Cells / Q000737:chemistry* / Q000502:physiology; D004730:Endothelium, Vascular / Q000737:chemistry* / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D007668:Kidney / Q000737:chemistry / Q000166:cytology; D008168:Lung / Q000737:chemistry / Q000166:cytology; D008954:Models, Biological; D009206:Myocardium / Q000737:chemistry / Q000166:cytology; D010446:Peptide Fragments / Q000276:immunology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D012501:Saphenous Vein / Q000737:chemistry / Q000166:cytology; D014841:von Willebrand Factor / Q000032:analysis
C115436:APLN protein, human; C104575:APLNR protein, human; D000906:Antibodies; D000073861:Apelin; D000075244:Apelin Receptors; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D043562:Receptors, G-Protein-Coupled; D014841:von Willebrand Factor