Accumulating evidence suggests that liver injury can be induced by the over-expression of β1-adrenergic receptors(β1-ARs).High titers of autoantibodies specific to β1-adrenergic receptors(β1-AA)are detected in the sera of heart failure patients,potentially playing agonist-like roles.However,the role of β1-AA in liver function has not been characterized.In this study,we collect the sera of primary biliary cholangitis(PBC)patients,a condition which easily develops into liver fibrosis,and analyze the relationship between PBC and β1-AA.A passive immunization model is established to assess the effect of β1-AA on the liver.Subsequently,the effect of β1-AA on macrophages is in-vestigated in vitro.Results show that PBC patients have a high titer and ratio of β1-AA,compared to controls.Liver injury and fibrosis are induced by β1-AA.In vitro experiments with ROS probe demonstrate that β1-AA induces macrophages to produce ROS and secrete TNFα.These effects can be partially reversed by metoprolol,a blocker forβ1-AR.Results from the transwell and phagocytosis assays show that β1-AA promotes macrophage migration and phagocytosis.FCM tests suggest that β1-AA induces the alteration of M1 rather than M2 markers in macrophages.Finally,the Annexin V/PI assay indicates that macrophage culture supernatants stimulated by β1-AA cause hepa-tocyte apoptosis.Overall,these results suggest that β1-AA is involved in PBC.The β1-AA-induced activation,pha-gocytosis and phenotypic modification of macrophages may play an important role in the development of hepatic fibrosis and injury.

Ye Wu;Xiongxiong Fan;Haicun Yu;Jingyi Liu;Yanru Duan;Suli Zhang;Li Yan;Yunhui Du;Huirong Liu

Department of Physiology and Pathophysiology,School of Basic Medical Sciences,Capital Medical University,Beijing 100069,China;Beijing key laboratory of metabolic disorder related cardiovascular disease,School of Basic Medical Sciences,Capital Medical University,Beijing 100069,China;Zhengzhou Central Hospital affiliated of Zhengzhou University,Zhengzhou 450000,China;Shanxi Cardiovascular Hospital,Cardiac Care Unit,Taiyuan 030024,China;Department of Pathophysiology,Institute of Basic Medical Science,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100005,China;Beijing Anzhen Hospital,Capital Medical University,Beijing Institute of Heart,Lung and Blood Vessel Diseases,Beijing100029,China

生物化学与生物物理学报（英文版）

[1]Ye Wu;Xiongxiong Fan;Haicun Yu;Jingyi Liu;Yanru Duan;Suli Zhang;Li Yan;Yunhui Du;Huirong Liu-.Macrophage polarization is involved in liver fibrosis induced by β1-adrenoceptor autoantibody)[J].生物化学与生物物理学报（英文版）,2022(08):1100-1112

tocyte,gocytosis

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