Putative Role for Apelin in Pressure/Volume Homeostasis and Cardiovascular Disease

Christopher   J.   Charles

Abstract

Apelin is a peptide recently isolated from bovine stomach extracts which appears to act as an endogenous ligand for the previously orphaned G-protein-coupled APJ receptor. The apelin gene encodes for a pre-propeptide consisting of 77 amino acids with mature apelin likely to be derived from the C-terminal region as either a 36, 17 or 13 amino acid peptide. Apelin mRNA expression and peptide immunoreactivity has been described in a variety of tissues including gastrointestinal tract, adipose tissue, brain, kidney, liver, lung and at various sites within the cardiovascular system. Apelin is strongly expressed in the heart with expression also present in the large conduit vessels, coronary vessels and endothelial cells. Message expression for the APJ receptor is similarly distributed throughout the brain and periphery, again including cardiovascular tissue. Consistent with this pattern of distribution, apelin and APJ have been shown to exhibit some role in the regulation of fluid homeostasis. In addition, a growing number of studies have reported cardiovascular actions of apelin. Not only has apelin been observed to alter arterial pressure, but the peptide also exhibits endotheliumdependent vasodilator actions in vivo and positive inotropic actions in the isolated heart. Furthermore, differences in apelin and APJ expression have been described in patients with congestive heart failure and circulating levels of apelin are also reported to change in heart failure. Taken together, these studies suggest a role for apelin in pressure/volume homeostasis and in the pathophysiology of cardiovascular disease. As such, manipulation of this peptide system may offer benefit to the syndrome of heart failure with potential clinical applications in humans.

Keywords: Apelin, APJ, arterial pressure, cardiovascular disease, heart failure, hypothalamo-pituitary-adrenal, peptide, vasoactive hormone