Predictive and therapeutic value of lipoprotein-associated phospholipaseA2 in sarcopenia in chronic obstructive pulmonary disease

<bold>Background:</bold> Sarcopenia, characterized by progressive muscle dysfunction, is a common complication of chronic obstructive pulmonary disease (COPD). Our previous study reported serum Lipoprotein-associated phospholipaseA2 (Lp-PLA2) level significantly increased in COPD and associated with exercise tolerance. This study further investigated the functions and target potential of Lp-PLA2 for sarcopenia in COPD. <bold>Methods:</bold> The serum Lp-PLA2 level/enzyme activity in patients with COPD and age-matched healthy subjects were detected. We explored the involvement of Lp-PLA2 in vivo and treatment efficacy of darapladib (a Lp-PLA2 specific inhibitor) in CS-induced muscle dysfunction models. <bold>Results:</bold> Compared with healthy control, serum Lp-PLA2 level/enzyme activity was elevated in COPD patients. In COPD patients, serum Lp-PLA2 level/enzyme activity significantly increased in patients with sarcopenia and negatively correlated with SMMI, quadriceps muscular strength, handgrip strength, thickness and cross-sectional area of the rectus femoris. In CS-induced muscle dysfunction C57BL/6 mice, up-regulated serum Lp-PLA2 level/enzyme activity was verified again. Darapladib treatment (25 and 50 mg/kg) rescued CS-induced muscle mass loss and muscle functions. Darapladib could reverse CS‐induced increase of atrogin‐1 and MuRF1 expression and activation of inflammatory factors, oxidant enzymes and NF-κB signaling. <bold>Conclusions:</bold> Serum Lp-PLA2 level was significantly elevated in patients with COPD, especially in sarcopenic patients with COPD, which could be a potential indicator for sarcopenia.