Apelin C-terminal fragments: biological properties and therapeutic potential

Abstract

The creation of bioactive molecules for the treatment of cardiovascular diseases based on natural peptides stimulates intensive experimental research. In recent years, it has been established that the C-terminal fragments of apelin, an endogenous ligand of the APJ receptor, reduce metabolic and functional disorders in experimental heart damage. The review presents literature data and generalized results of our own experiments on the effect of apelin-13, [Pyr]apelin-13, apelin-12, and their chemically modified analogues on the heart in normal conditions and when modeling pathophysiological conditions in vitro and in vivo. It has been shown that the spectrum of action of apelin peptides on the damaged myocardium covers a decrease in the death of cardiomyocytes from necrosis, a decrease in cardiomyocyte membrane damage, an improvement in the metabolic state of the myocardium, and a decrease in the formation of reactive oxygen species and lipid peroxidation products. The mechanisms of the protective action of these peptides associated with the activation of the APJ receptor and the manifestation of antioxidant properties are discussed. The data presented in the review indicate the promise of molecular design of pharmacological APJ receptor agonists, which can serve as the basis for the development of cardioprotectors that affect the processes of free radical oxidation and metabolic adaptation.