Cardioprotective apelin effects and the cardiac-renal axis: review of existing science and potential therapeutic applications of synthetic and native regulated apelin

First described in 1998, apelin is one of the endogenous ligands of the apelinergic receptor. Since its discovery, its possible role in human physiology and disease has been intensively studied. Apelin is a native cardioprotective agent that the body synthesizes to create atheroprotective, antihypertensive, and regenerative effects in the body. By antagonizing the RAA system, apelin could play an important role in heart failure and hypertension. It is also involved in myocardial protection against ischemia/reperfusion injury, post-ischemic remodeling, and myocardial fibrosis. A small number of studies even suggest that serum apelin levels may be involved the development of life-threatening arrhythmias. All this information generated excitement about potential therapeutic effects in patients with heart failure and myocardial infarction. The therapeutic index of apelin is unknown but is anticipated to be favorable based on the small number of studies. In this review, we summarize the mechanisms by which apelin exerts its cardioprotective effects and its connection with the cardiorenal axis. Also, we report the potential therapeutic applications of synthetic and native regulated apelin. If larger studies can be performed, it is possible that apelin-mediated drug treatment may play a major role for a large number of patients worldwide in the future.