Targeting the apelin system for the treatment of cardiovascular diseases.

Cardiovascular disease is the leading cause of death worldwide. Its prevalence is rising due to ageing populations and the increasing incidence of diseases such as chronic kidney disease, obesity, and diabetes that are associated with elevated cardiovascular risk. Despite currently available treatments, there remains a huge burden of cardiovascular disease-associated morbidity for patients and healthcare systems, and newer treatments are needed. The apelin system, comprising the apelin receptor and its two endogenous ligands apelin and elabela, is a broad regulator of physiology that opposes the actions of the renin-angiotensin and vasopressin systems. Activation of the apelin receptor promotes endothelium-dependent vasodilatation and inotropy, lowers blood pressure, and promotes angiogenesis. The apelin system appears to protect against arrhythmias, inhibits thrombosis, and has broad anti-inflammatory and anti-fibrotic actions. It also promotes aqueous diuresis through direct and indirect (central) effects in the kidney. Thus, the apelin system offers therapeutic promise for a range of cardiovascular, kidney, and metabolic diseases. This review will discuss current cardiovascular disease targets of the apelin system and future clinical utility of apelin receptor agonism. ; This work was supported by Kidney Research UK (TF_006_20171124 to F.A.C.); British Heart Foundation (TG/18/4/33770 to A.P.D. and J.J.M., FS/06/064, FS/09/019, CH09/002, RG/16/10/32375, RE/18/5/34216 to D.E.N.); National Institute for Health and Care Research Cambridge Biomedical Research Centre Biomedical Resources Grant (A.P.D. and J.J.M.); Wellcome Trust (WT103782AIA to D.E.N.); and Chief Scientist Office (SCAF/19/02 to N.D.). The views expressed are those of the authors and not necessarily those of the National Institute for Health and Care Research or the Department of Health and Social Care.