Roles And Mechanisms Of Apelin In Pulmonary Hypertension And Acute Lung Injury

Background:Apelin was found in 1998 to be a cognate endogenous ligand for the APJ receptor (a putative receptor protein related to the angiotensin-type 1 receptor), which previously had been designated an "orphan" G-protein-coupled receptor (GPCRs) and first identified by the Human Genome Project. The structure of apelin and APJ is highly conserved among species, suggesting its important physiological roles. It is well known that GPCRs are important regulators of cardiovascular and pulmonary physiology and represent the greatest proportion of known therapeutic targets. Therefore, the association of novel G protein signaling pathways with human disease of cardio-pulmonary system is of great importance. In rats, mice and humans, messenger RNA encoding both APJ and apelin. as well as the respective peptides, is abundantly expressed in the central nervous and peripheral tissues, which suggests their intensive biological functions of this signaling pathway. Several studies have showed that apelin might play a role in regulating fluid homeostasis and immune function, inhibiting human immunodeficiency virus infection by blocking the virus coreceptor However, expression studies in animal tissues clearly revealed that the lung is the site of strongest expression both of apelin and APJ, followed by heart, suggesting apelin and APJ system might have an important physiological role and pathophysiological significance in pulmonary and cardiovascular system. Some studies showed that intravenous injection of apelin decreased blood pressure and apelin had positive inotropic effects in vivo in both normal and failing hearts of rats. Left ventricular expression of APJ mRNA was markedly reduced in patients with idiopathic dilated cardiomyopathy. Reduced plasma apelin levels were observed in patients with lone atrial fibrillation. In a rat model of myocardial injury, apelin had a cardioprotective effect, which was directly related to the decrease of lipid peroxidation.To date, however, there is little information on the functional roles of apelin and APJ in pulmonary circulation, nor is there any information on pathogenesis of pulmonary...