• Xiao-Fang Fan, Feng Xue, Yue-Qi Zhang, Xue-Ping Xing, Hui Liu, Sun-Zhong Mao, Xiao-Xia Kong, Yu-Qi Gao, Shu F Liu, and Yong-Sheng Gong.
• Chest. 2015 Apr 1;147(4):969-78.

BackgroundAlthough the mechanisms and pathways mediating ARDS have been studied extensively, less attention has been given to the mechanisms and pathways that counteract injury responses. This study found that the apelin-APJ pathway is an endogenous counterinjury mechanism that protects against ARDS.MethodsUsing a rat model of oleic acid (OA)-induced ARDS, the effects of ARDS on apelin and APJ receptor expressions and on APJ receptor binding capacity were examined. The protective effect of activating the apelin-APJ pathway against OA- or lipopolysaccharide (LPS)-induced ARDS was evaluated.ResultsARDS was coupled to upregulations of the apelin and APJ receptor. Rats with OA-induced ARDS had higher lung tissue levels of apelin proprotein and APJ receptor expressions; elevated plasma, BAL fluid (BALF), and lung tissue levels of apelin-36 and apelin-12/13; and an increased apelin-APJ receptor binding capacity. Upregulation of the apelin-APJ system has important pathophysiologic function. Stimulation of the apelin-APJ signaling using receptor agonist apelin-13 alleviated, whereas inhibition of the apelin-APJ signaling using receptor antagonist [Ala]-apelin-13 exacerbated, OA-induced lung pathologies, extravascular lung water accumulation, capillary-alveolar leakage, and hypoxemia. The APJ receptor agonist inhibited, and the APJ receptor antagonist augmented, OA-induced lung tissue and BALF levels of tumor necrosis factor-α and monocyte chemoattractant protein-1, and plasma and lung tissue levels of malondialdehyde. Postinjury treatment with apelin-13 alleviated lung inflammation and injury and improved oxygenation in OA- and LPS-induced lung injury.ConclusionsThe apelin-APJ signaling pathway is an endogenous anti-injury and organ-protective mechanism that is activated during ARDS to counteract the injury response and to prevent uncontrolled lung injury.

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