Meteorin-like protein elevation post-exercise improved vascular inflammation among coronary artery disease patients by downregulating NLRP3 inflammasome activity

Abstract

Background: Coronary artery disease (CAD) has become the most common cause of death worldwide. However, the negative effects of CAD are able to be alleviated via exercises, possibly via increased production of meteorin-like protein (Metrnl). In this study, we aim to evaluate the connection between Metrnl production during exercise with lowered CAD risk and severity. Methods: Two age and gender-matched groups of 60 human patients, one with CAD, and one without were randomly recruited. The CAD group were subjected to continuous training exercises. Mice were exercised by using a treadmill, establishing an animal exercise model. ELISA was used to measure plasma Metrnl and inflammatory factors. To determine the impact of Metrnl on glucose metabolism, oxygen consumption and extracellular acid rates were taken for untreated, palmitic acid (PA)-treated, and PA+Metrnl co-treated human umbilical vein endothelial cells. Western blot was used to measure expression levels for the NLR family pyrin domain containing 3 inflammasome. Results: CAD patients had lower Metrnl levels compared to non-CAD controls. Furthermore, higher Metrnl levels post-exercise were inversely associated with LDL, inflammatory cytokines, and CAD severity, as well as being positively associated with HDL. Metrnl was able to counteract against PA-induced HUVEC glucose metabolic dysfunction via reducing ROS production, which in turn lowered NLRP3 inflammasome expression, thereby serving as the basis behind the inverse correlation between Metrnl and inflammatory cytokines. Conclusions: Exercise was able to increase Metrnl production from skeletal muscle among CAD patients, and subsequently improve patient atherosclerosis via counteracting against endothelial metabolic dysfunction and pro-inflammatory activities.