α1-AR overactivation induces cardiac inflammation through NLRP3 inflammasome activation

查看全文 作　　者：Jun-zhou [1,2]Xin;Ji-min [2]Wu;Guo-min [2]Hu;Hui-jun [2,3]Gu;Ye-nan [2]Feng;Shuai-xing [2]Wang;Wen-wen [2,4]Cong;Ming-zhe [2]Li;Wen-li [2]Xu;Yao [2]Song;Han [2]Xiao;You-yi [2]Zhang;Li [1]Wang

机构地区：[1]The 3rd Department of Cardiology,The First Affiliated Hospital of the Medical College,Shihezi University,Shihezi 832008,China;[2]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,Beijing 100191,China;[3]Academy for Advanced Interdisciplinary Studies,Peking University,Beijing 100871,China;[4]Key Laboratory of Xinjiang Endemic and Ethnic Diseases,Department of Physiology,School of Medicine Shihezi University,Shihezi 832000,China

出　　处：《Acta Pharmacologica Sinica》索引2020年第41卷第3期,共8页

基　　金：This work was supported by grants from the National Natural Science Foundation of China(81260028 to Li Wang,No.81530009 to You-yi Zhang and No.81670205 to Han Xiao);the Fund for Fostering Young Scholars of Peking University Health Science Center(No.BMU2017PY016 to Han Xiao);the Open Foundation from Beijing Key Laboratory of Hypertension Research(No.2017GXY-KFKT-05 to Han Xiao). 摘　　要：Acute sympathetic stress causes excessive secretion of catecholamines and induces cardiac injuries,which are mainly mediated byβ-adrenergic receptors(β-ARs).However,α1-adrenergic receptors(α1-ARs)are also expressed in the heart and are activated upon acute sympathetic stress.In the present study,we investigated whetherα1-AR activation induced cardiac inflammation and the underlying mechanisms.Male C57BL/6 mice were injected with a single dose ofα1-AR agonist phenylephrine(PE,5 or 10 mg/kg,s.c.)with or without pretreatment withα-AR antagonist prazosin(5 mg/kg,s.c.).PE injection caused cardiac dysfunction and cardiac inflammation,evidenced by the increased expression of inflammatory cytokine IL-6 and chemokines MCP-1 and MCP-5,as well as macrophage infiltration in myocardium.These effects were blocked by prazosin pretreatment.Furthermore,PE injection significantly increased the expression of NOD-like receptor protein 3(NLRP3)and the cleavage of caspase-1(p20)and interleukin-18 in the heart;similar results were observed in both Langendorff-perfused hearts and cultured cardiomyocytes following the treatment with PE(10μM).Moreover,PE-induced NLRP3 inflammasome activation and cardiac inflammation was blocked in Nlrp3-/-mice compared with wild-type mice.In conclusion,α1-AR overactivation induces cardiac inflammation by activating NLRP3 inflammasomes. 关键词：α1-adrenergic RECEPTOR CARDIAC INFLAMMATION NOD-like RECEPTOR protein 3 INFLAMMASOME caspase-1 interleukin-18 PHENYLEPHRINE PRAZOSIN

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α1-AR overactivation induces cardiac inflammation through NLRP3 inflammasome activation

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