Role of Apelin/Apelin Receptor Axis in Heart Disease: Therapeutic role of Apelin Analogues

The apelin peptide system is widely distributed throughout the human body and is a critical mediator of cardiovascular homeostasis. Activation of the apelin receptor by its cognate peptide ligand, apelin, induces a wide... [ view full abstract ]

The apelin peptide system is widely distributed throughout the human body and is a critical mediator of cardiovascular homeostasis. Activation of the apelin receptor by its cognate peptide ligand, apelin, induces a wide range of physiological effects, including vasodilationx of cardiac contractility, angiogenesis, and regulation of energy metabolism and fluid homeostasis. The apelin/apelin receptor is also implicated in pathologies including atherosclerosis, hypertension, coronary heart disease, heart failure, diabetes, obesity, and cancer, making it a promising therapeutic target. Considering the potential therapeutic effects by modulation of the apelin/apelin receptor system, research is expanding to develop novel therapies that inhibit degradation of endogenous apelin peptides and augment stable agonists and antagonists to more efficiently interfere in the apelin/apelin receptor system. Given the role of apelin/apelin receptor in cardiovascular diseases, an increased understanding of the cardiovascular actions of apelin/apelin receptor system will help to develop novel therapeutic interventions for cardiovascular diseases. The apelin/apelin receptor signaling represent a relatively new therapeutic axis for the potential treatment of cardiovascular disease. Angiotensin converting enzyme 2 (ACE2) and neutral endopeptidase (NEP) are two key proteases which cleaves and inactivates apelin peptides. The ability of NEP inhibition to can explain the therapeutic benefits of the newly approved heart failure therapy, LCZ696 (EntrestoTM), whch includes the NEP inhibitor, sacubitril. We have designed and synthesized novel and potent apelin analogues which are resistant to degradation by proteases as potential drugs for cardiovascular diseases.