Roles And Mechanisms Of Apelin In Pulmonary Hypertension

【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.【Objective】To explore the change and significance of vasoactive peptide Apelin and its receptor APJ during pulmonary hypertension and acute lung injury,and the effect of Apelin on acute lung injury induced by oleic acid.【Methods】(1)To explore the change of plasma apelin and its role in patients with pulmonary hypertension(PH),18 patients with PH(PH group,12 cases complicating chronic Cor Pulmonale)and 21 healthy volunteers(normal control,NC group)were enrolled in the study. The levels of peripheral venous plasma apelin were measured by radioimmunoassay.The pulmonary arterial systolic pressure(PASP)of PH group was measured by echocardiography with Doppler ultrasound.(2)Rat pulmonary hypertension was induced by hypoxia(FiO₂ 9%～11%,FiCO₂＜3%,8hours/day,6days/week);Immunohistochemistry to observe the localization of Apelin and APJ in pulmonary arterioles.【Results】(1)There are significant differences of the plasma Apelin concentration between PH group(67.11±16.67 pg/mL)and NC group(94.52±15.90 pg/mL),But we still can not draw a conclusion that the plasma Apelin content was correlated with PASP;(2)The influence of hypoxia on Apelin contents in the pulmonary tissues showed biphasic changes(1H group lower and 4H group higher,compared with NC group).【Conclusions】The marked,decrease of Apelin in plasma of patients in PH group may suggest a relationship between them.But the correlation was not found exactly;Hypoxia affected the distribution of apelin in pulmonary arterioles,decreased expression in endothelial lineage and increased expression in adventitium,and further study must be need.