Galectin-3-centered paracrine network mediates cardiac inflammation and fibrosis upon β-adrenergic insult  

作　　者：Guomin Hu Jimin Wu Huijun Gu Xiangning Deng Wenli Xu Shan Feng Shuaixing Wang Yao Song Zhengda Pang Xiuling Deng Aleksandr E.Vendrov Nageswara R.Madamanchi Marschall S.Runge Xinyu Wang Youyi Zhang Han Xiao Erdan Dong 

机构地区：[1]Department of Cardiology and Institute of Vascular Medicine,Peking University Third Hospital,NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides,Key Laboratory of Molecular Cardiovascular Science,Ministry of Education,Beijing Key Laboratory of Cardiovascular Receptors Research,Research Unit of Medical Science Research Management/Basic and Clinical Research of Metabolic Cardiovascular Diseases,Chinese Academy of Medical Sciences,Beijing 100191,China [2]Department of Physiology and Pathophysiology,Cardiovascular Research Center,School of Basic Medical Sciences,Xi’an Jiaotong University Health Science Center,Xi’an 710061,China [3]Department of Internal Medicine,Frankel Cardiovascular Center,University of Michigan,Ann Arbor,MI,48109,USA [4]Academy for Advanced Interdisciplinary Studies,Peking University,Beijing 100087,China

出　　处：《Science China(Life Sciences)》2023年第5期1067-1078,共12页中国科学（生命科学英文版）

基　　金：supported by the National Key R&D Program of China (2021YFF0501401);the National Natural Science Foundation of China (82030072);the Michigan Medicine-PKUHSC Joint Institute for Translational and Clinical Research (BMU2019JI007);the Fundamental Research Funds for the Central Universities;the National Natural Science Foundation of China (81830009, 81822003);the Beijing Municipal Natural Science Foundation (7191013);the Key Clinical Projects of Peking University Third Hospital (BYSYZD2019022);CAMS Innovation Fund for Medical Sciences to (2021-I2M-5-003)。

摘　　要：Rapid over-activation of β-adrenergic receptors (β-AR) following acute stress initiates cardiac inflammation and injury by activating interleukin-18 (IL-18),however,the process of inflammation cascades has not been fully illustrated.The present study aimed to determine the mechanisms of cardiac inflammatory amplification following acute sympathetic activation.With bioinformatics analysis,galectin-3 was identified as a potential key downstream effector of β-AR and IL-18 activation.The serum level of galectin-3 was positively correlated with norepinephrine or IL-18 in patients with chest pain.In the heart of mice treated with β-AR agonist isoproterenol (ISO,5 mg kg^(-1)),galectin-3 expression was upregulated markedly later than IL-18 activation,and Nlrp3^(-/-)and Il18^(-/-)mice did not show ISO-induced galectin-3 upregulation.It was further revealed that cardiomyocyte-derived IL-18 induced galectin-3 expression in macrophages following ISO treatment.Moreover,galectin-3deficiency suppressed ISO-induced cardiac inflammation and fibrosis without blocking ISO-induced IL-18 increase.Treatment with a galectin-3 inhibitor,but not a β-blocker,one day after ISO treatment effectively attenuated cardiac inflammation and injury.In conclusion,galectin-3 is upregulated to exaggerate cardiac inflammation and injury following acute β-AR activation,a galectin-3 inhibitor effectively blocks cardiac injury one day after β-AR insult.

关 键 词：GALECTIN-3 interleukin-18 β-adrenergic receptor macrophage INFLAMMATION FIBROSIS 

分 类 号：R54[医药卫生—心血管疾病]