Apelin, the endogenous
ligand for the
G-protein-coupled APJ receptor, is emerging as a key
hormone in cardiovascular homoeostasis. It is expressed in a diverse range of tissues with particular preponderance for the cardiovascular system, being found in both the heart and vasculature.
Apelin is the most potent in vitro inotrope yet identified and causes endothelium- and
nitric oxide-dependent vasodilatation. It also appears to have a role in
lipid and
glucose metabolism as well as fluid homoeostasis. One of the key emerging features of the
apelin--APJ system is its interaction with the renin-angiotensin system with the respective receptors sharing marked sequence homology, forming heterodimers, and mediating opposing physiological actions. To date, both preclinical and limited clinical studies suggest that the
apelin--APJ system may have an important role in the pathogenesis of
heart failure. Although the
apelin--APJ system is downregulated, the inotropic actions of
apelin persist and are enhanced in failing hearts without inducing ventricular
hypertrophy. In combination with its interaction with the renin-angiotensin system, APJ agonism may provide a new therapeutic target in the treatment of acute and chronic
heart failure. In this review, we highlight key aspects of the
apelin--APJ system in health and disease, and consider its translational and therapeutic potential. The diverse actions of the
apelin--APJ system have implications for understanding the pathophysiology of, and development of treatments for, several major
cardiovascular diseases.