Apelin is the endogenous peptide ligand for the G-protein-coupled APJ receptor, which is expressed in various organs such as the heart, vasculature, kidney, adipose tissue, endothelium, and human plasma.
Lanthio Pharma is working on the discovery of lanthipeptide stabilized versions of apelin, with attractive potential as treatment for Heart Failure.
Vascular expression of the receptor participates in the control of blood pressure and its activation promotes the formation of new blood vessels (angiogenesis).
Studies in mice knocked out for the apelin receptor gene suggest a balance between angiotensin II signalling, which increases blood pressure and apelin signalling, which lowers blood pressure.
The angiogenic activity is the consequence of apelin action on the proliferation and migration of the endothelial cells. Apelin activates transduction cascades which lead to the proliferation of endothelial cells and the formation of new blood vessels.
Apelin receptors are expressed in cardiomyocytes where apelin behaves as one of the most potent stimulator of cardiac contractility. Aged apelin knockout mice develop progressive impairment of cardiac contractility. Apelin levels are increased in left ventricles of patients with chronic heart failure.
In addition, apelin regulates fluid homeostasis via active water excretion in the kidney.
Insulin exerts a positive action on adipocyte apelin production. In pancreas, apelin inhibits the insulin secretion induced by glucose. This inhibition reveals the functional interdependency between apelin signalling and insulin signalling observed at the adipocyte level. Recently, receptor expression was also detected in skeletic muscle cells. Its activation is involved in glucose uptake and may be related to insulin resistance.