Effect of Apelin-APJ system in postischaemic myocardial protection: a pharmacological postconditioning tool?

In the heart a great part of ischaemia and reperfusion injuries occurs mainly during the first minutes of reperfusion. The opening of the mitochondrial permeability transition pores is the end point of the cascade to myocardial damage. Also oxidative stress contributes to cell death. Postconditioning is a protective maneuver that can be selectively timed at the beginning of reperfusion. It is hypothesized that it acts via the reperfusion injury salvage kinase (RISK) pathway which includes NO-dependent and NO-independent cascades. Apelin is an endogenous peptide which can protect the heart from reperfusion injury if given at the beginning of reperfusion but not before ischaemia. It is hypothesized that it may trigger the RISK pathway via a specific APJ receptor. Apelin can limit the oxidative stress also by the activation of superoxide dismutase. Apelin and APJ expression increase early after ischaemia and at the beginning of an ischaemic heart failure. These observations suggest that the endogenous release of the peptide can limit the severity of an infarction and ameliorate myocardial contractility compromised by the appearance of the failure. Due to its protective activities, apelin could be a therapeutic tool if administered with the same catheter used for angioplasty or after the maneuvers aimed at bypassing a coronary occlusion.