Modulation of the apelin/APJ system in heart failure and atherosclerosis in man.
OBJECTIVE
The aim of this study was to determine whether the apelin/APJ system is altered in human cardiovascular disease by investigating whether the expression of apelin or its receptor is altered at the protein level.


METHODS
Radioligand binding studies were used to determine apelin receptor density in human cardiac tissues. Apelin peptide levels in cardiovascular tissues were determined by radioimmunoassay. In vitro pharmacology was used to assess vasoactive properties of apelin in human coronary artery. Localization of apelin and its receptor in coronary artery was determined using immunohistochemistry.


RESULTS
Apelin receptor density was significantly decreased in left ventricle from patients with dilated cardiomyopathy or ischaemic heart disease compared with controls, but apelin peptide levels remained unchanged. Apelin was up-regulated in human atherosclerotic coronary artery and this additional peptide localized to the plaque, colocalizing with markers for macrophages and smooth muscle cells. Apelin potently constricted human coronary artery.


CONCLUSIONS
We have detected changes in the apelin/APJ system in human diseased cardiac and vascular tissue. The decrease in receptor density in heart failure may limit the positive inotropic actions of apelin, contributing to contractile dysfunction. The contribution of the increased apelin levels in atherosclerotic coronary artery to disease progression remains to be determined. These data suggest a potential role for the apelin/APJ system in human cardiovascular disease.
Pitkin
Sarah L
SL
Clinical Pharmacology Unit, University of Cambridge, Level 6 Centre for Clinical Investigation, Box 110 Addenbrooke's Hospital, Cambridge, UK.
Maguire
Janet J
JJ
Kuc
Rhoda E
RE
Davenport
Anthony P
AP
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000073861:Apelin; D000075244:Apelin Receptors; D002311:Cardiomyopathy, Dilated / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000378:metabolism*; D003331:Coronary Vessels / Q000378:metabolism; D005260:Female; D006333:Heart Failure / Q000378:metabolism*; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000378:metabolism*; D011863:Radioimmunoassay; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D055815:Young Adult
C115436:APLN protein, human; C104575:APLNR protein, human; D000073861:Apelin; D000075244:Apelin Receptors; D036341:Intercellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled