Wenhua Sun1, Yingying Lin1, Liling Chen2, Rong Ma1, Jiayu Cao1, Jing Yao1, Kaihong Chen2, Jieqing Wan3. 1. Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, People's Republic of China. 2. Department of Cardiology, Longyan First Hospital affiliated to Fujian Medical University, Fujian 364000, People's Republic of China. 3. Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, People's Republic of China. Electronic address: jieqingwan@126.com.
Abstract
OBJECTIVE: Autophagy plays a prominent role in the pathogenesis of plaques formation and progression of atherosclerosis (AS). The cysteine protease legumain is known to participate in atherogenesis, but its function and underlying mechanism in AS macrophages remain unclear. METHODS: The expressions of legumain in plaques isolated from AS patients and in macrophages stimulated with oxLDL were examined. Moreover, we effectively altered legumain expression in macrophages to characterize the effect of legumain on oxLDL-induced macrophage apoptosis. The expression of apoptotic and autophagic factors was analysed. RESULTS: Legumain was present in plaques, and its expression was upregulated in macrophages treated with oxLDL. Suppressing legumain significantly increased oxLDL-induced macrophage apoptosis and the expression of caspase 3, caspase 9 and Bax. However, legumain overexpression decreased macrophage apoptosis upon oxLDL exposure and the levels of caspase 3, caspase 9 and Bax. In addition, recombinant legumain protein suppressed macrophage apoptosis. Biochemical experiments revealed that legumain deficiency decreased the levels of Beclin1 and LC3, whereas increased legumain expression increased the levels of Beclin1 and LC3 significantly. CONCLUSION: Legumain regulates oxLDL-induced macrophage apoptosis by enhancing the autophagy pathway, which may also influence the vulnerability of atherosclerotic plaques.
OBJECTIVE: Autophagy plays a prominent role in the pathogenesis of plaques formation and progression of atherosclerosis (AS). The cysteine protease legumain is known to participate in atherogenesis, but its function and underlying mechanism in AS macrophages remain unclear. METHODS: The expressions of legumain in plaques isolated from AS patients and in macrophages stimulated with oxLDL were examined. Moreover, we effectively altered legumain expression in macrophages to characterize the effect of legumain on oxLDL-induced macrophage apoptosis. The expression of apoptotic and autophagic factors was analysed. RESULTS:Legumain was present in plaques, and its expression was upregulated in macrophages treated with oxLDL. Suppressing legumain significantly increased oxLDL-induced macrophage apoptosis and the expression of caspase 3, caspase 9 and Bax. However, legumain overexpression decreased macrophage apoptosis upon oxLDL exposure and the levels of caspase 3, caspase 9 and Bax. In addition, recombinant legumain protein suppressed macrophage apoptosis. Biochemical experiments revealed that legumain deficiency decreased the levels of Beclin1 and LC3, whereas increased legumain expression increased the levels of Beclin1 and LC3 significantly. CONCLUSION:Legumain regulates oxLDL-induced macrophage apoptosis by enhancing the autophagy pathway, which may also influence the vulnerability of atherosclerotic plaques.