Apelin, the endogenous
ligand of the
G protein-coupled APJ receptor, is a
peptide mediator with emerging regulatory actions in the heart. We aimed to determine whether the endogenous
apelin/APJ system is an intrinsic protective pathway in ischemic/
reperfusion injury. A Langendorff model of perfused isolated rat hearts and primary cultured myocardial cells from neonatal rats were used. Cardiac function was monitored and
apelin/APJ expression was determined by real-time PCR and Western blot analysis. In rats under I/R, cardiac function was significantly decreased as compared with controls, and APJ was over-expressed at both the
mRNA and
protein levels (by 7-fold and 35%, respectively, both p<0.01). However, pre-administration of
apelin (30pmol/L) greatly ameliorated the reduced heart function. To gain mechanistic insight into the cardio-protective effects of
apelin/APJ, cultured cardiomyocytes were treated with
apelin (30 pmol/L), and those under
hypoxia/re-oxygenation showed H/R-induced apoptosis and up-regulated
apelin/APJ
mRNA expression by 6-fold and 7-fold, respectively (both p<0.01). And
lactate dehydrogenase leakage was greatly increased as well. Meanwhile, apoptosis, the generation of
reactive oxygen species and
malonaldehyde content as well as
lactate dehydrogenase leakage were inhibited by
apelin. Furthermore,
apelin enhanced
superoxide dismutase activity and phosphorylation of
extracellular signal-regulated kinase 1/2 and Akt after
hypoxia/re-oxygenation. In conclusion,
apelin/APJ has protective effects in
ischemic heart disease and might constitute an important
therapy target.