TY - JOUR
T1 - The apelin-APJ system in heart failure
T2 - pathophysiologic relevance and therapeutic potential
AU - Japp, Alan G
AU - Newby, David E
PY - 2008/5
Y1 - 2008/5
N2 - Apelin is the endogenous ligand for the previously orphaned G protein-coupled receptor, APJ. This novel peptidic signalling pathway is widely represented in the heart and vasculature, and is emerging as an important regulator of cardiovascular homeostasis. In preclinical models, apelin causes nitric oxide-dependent vasodilatation, reduces ventricular preload and afterload, and increases cardiac contractility in rats with normal and failing hearts. Apelin-APJ signalling also attenuates ischemic myocardial injury and maintains cardiac performance in ageing and chronic pressure overload. Downregulation of apelin and APJ expression coincides with declining cardiac performance raising the possibility that diminished apelin-APJ activity may have pathophysiologic implications. At present, data from human studies is limited but changes in apelin and APJ expression in patients with chronic heart failure parallel those seen in preclinical models. Detailed clinical investigation is now required to establish the role of apelin in human cardiovascular physiology and pathophysiology, and to determine the therapeutic potential of augmenting apelin signalling in patients with heart failure.
AB - Apelin is the endogenous ligand for the previously orphaned G protein-coupled receptor, APJ. This novel peptidic signalling pathway is widely represented in the heart and vasculature, and is emerging as an important regulator of cardiovascular homeostasis. In preclinical models, apelin causes nitric oxide-dependent vasodilatation, reduces ventricular preload and afterload, and increases cardiac contractility in rats with normal and failing hearts. Apelin-APJ signalling also attenuates ischemic myocardial injury and maintains cardiac performance in ageing and chronic pressure overload. Downregulation of apelin and APJ expression coincides with declining cardiac performance raising the possibility that diminished apelin-APJ activity may have pathophysiologic implications. At present, data from human studies is limited but changes in apelin and APJ expression in patients with chronic heart failure parallel those seen in preclinical models. Detailed clinical investigation is now required to establish the role of apelin in human cardiovascular physiology and pathophysiology, and to determine the therapeutic potential of augmenting apelin signalling in patients with heart failure.
U2 - 10.1016/j.bcp.2007.12.015
DO - 10.1016/j.bcp.2007.12.015
M3 - Article
C2 - 18272138
VL - 75
SP - 1882
EP - 1892
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
SN - 0006-2952
IS - 10
ER -