SGLT2 inhibitor, canagliflozin, ameliorates cardiac inflammation in experimental autoimmune myocarditis

被引：33
作者：
Long, Qi [1 ]
Li, Lixia [1 ]
Yang, Hongmin [1 ]
Lu, Yang [1 ]
Yang, Han [1 ]
Zhu, Yaoxi [1 ]
Tang, Yaohan [1 ]
Liu, Changhu [1 ]
Yuan, Jing [1 ]
机构：
[1] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Cardiol, Jie Fang Ave 1277, Wuhan 430022, Peoples R China
来源：
INTERNATIONAL IMMUNOPHARMACOLOGY | 2022年 / 110卷
关键词：
Canagliflozin; SGLT2i; Myocarditis; NLRP3; inflammasome; Th17 cell differentiation; Apoptosis; ACTIVATION; CARDIOMYOPATHY; INTERLEUKIN-1; APOPTOSIS; PROTECTS; DEATH; CELLS;
D O I：
10.1016/j.intimp.2022.109024
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Myocarditis is an inflammatory cardiovascular disease which contributes to dilated cardiomyopathy (DCM) and heart failure. Canagliflozin (CANA) exerts anti-inflammatory and cardioprotective effects in heart failure besides its hypoglycemic effect. However, the role of CANA in myocarditis has not been elucidated. In this work, CANA treatment markedly alleviated cardiac inflammation and improved cardiac function in experimental autoimmune myocarditis (EAM) mice induced by a-myosin-heavy chain peptides. The expressions of NLRP3 inflammasome complexes (NLRP3, ASC, and Caspase-1) and their downstream molecules (IL-113, IL-18) were significantly downregulated by CANA, accompanied with reduced Th17 cell infiltration in hearts. Furthermore, Bax/Bcl-2 ratio, Cleaved Caspase-3 protein level and the percentage of TUNEL-positive myocardial cells, which usually indicated apoptosis, were reduced by CANA treatment. These findings suggest CANA could be a valuable medication for myocarditis treatment.
引用
收藏
页数：10
相关论文
共 50 条
[1]   Interleukin-1 and the Inflammasome as Therapeutic Targets in Cardiovascular Disease [J].
Abbate, Antonio ;
Toldo, Stefano ;
Marchetti, Carlo ;
Kron, Jordana ;
Van Tassell, Benjamin W. ;
Dinarello, Charles A. .
CIRCULATION RESEARCH, 2020, 126 (09) :1260-1280
[2]   Apoptosis in Patients With Acute Myocarditis [J].
Abbate, Antonio ;
Sinagra, Gianfranco ;
Bussani, Rossana ;
Hoke, Nicholas N. ;
Merlo, Marco ;
Varma, Arnit ;
Toldo, Stefano ;
Salloum, Fadi N. ;
Biondi-Zoccai, Giuseppe G. L. ;
Vetrovec, George W. ;
Crea, Filippo ;
Silvestri, Furio ;
Baldi, Alfonso .
AMERICAN JOURNAL OF CARDIOLOGY, 2009, 104 (07) :995-1000
[3]   SGLT1 is a novel cardiac glucose transporter that is perturbed in disease states [J].
Banerjee, Sanjay K. ;
McGaffin, Kenneth R. ;
Pastor-Soler, Nuria M. ;
Ahmad, Ferhaan .
CARDIOVASCULAR RESEARCH, 2009, 84 (01) :111-118
[4]   Empagliflozin Protects against Diet-Induced NLRP-3 Inflammasome Activation and Lipid Accumulation [J].
Benetti, Elisa ;
Mastrocola, Raffaella ;
Vitarelli, Giovanna ;
Cutrin, Juan Carlos ;
Nigro, Debora ;
Chiazza, Fausto ;
Mayoux, Eric ;
Collino, Massimo ;
Fantozzi, Roberto .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2016, 359 (01) :45-53
[5]   Empagliflozin Blunts Worsening Cardiac Dysfunction Associated With Reduced NLRP3 (Nucleotide-Binding Domain-Like Receptor Protein 3) Inflammasome Activation in Heart Failure [J].
Byrne, Nikole J. ;
Matsumura, Nobutoshi ;
Maayah, Zaid H. ;
Ferdaoussi, Mourad ;
Takahara, Shingo ;
Darwesh, Ahmed M. ;
Levasseur, Jody L. ;
Jahng, James Won Suk ;
Vos, Dyonne ;
Parajuli, Nirmal ;
El-Kadi, Ayman O. S. ;
Braam, Branko ;
Young, Martin E. ;
Verma, Subodh ;
Light, Peter E. ;
Sweeney, Gary ;
Seubert, John M. ;
Dyck, Jason R. B. .
CIRCULATION-HEART FAILURE, 2020, 13 (01) :E006277
[6]   The Severity of CVB3-Induced Myocarditis Can Be Improved by Blocking the Orchestration of NLRP3 and Th17 in Balb/c Mice [J].
Chen, Jifei ;
Yang, Fan ;
Shi, Song ;
Liu, Xuexiang ;
Qin, Fengxian ;
Wei, Xiaomou ;
Huang, Yujie ;
Liang, Wenwu ;
Miao, Lin .
MEDIATORS OF INFLAMMATION, 2021, 2021
[7]   Sudden cardiac death in young people with apparently normal heart [J].
Corrado, D ;
Basso, C ;
Thiene, G .
CARDIOVASCULAR RESEARCH, 2001, 50 (02) :399-408
[8]   Trends in myocarditis incidence, complications and mortality in Sweden from 2000 to 2014 [J].
Fu, Michael ;
Kontogeorgos, Silvana ;
Thunstrom, Erik ;
Sandstrom, Tatiana Zverkova ;
Kroon, Christian ;
Bollano, Entela ;
Schaufelberger, Maria ;
Rosengren, Annika .
SCIENTIFIC REPORTS, 2022, 12 (01)
[9]   Molecular mimicry, bystander activation, or viral persistence: Infections and autoimmune disease [J].
Fujinami, RS ;
von Herrath, MG ;
Christen, U ;
Whitton, JL .
CLINICAL MICROBIOLOGY REVIEWS, 2006, 19 (01) :80-+
[10]   Canagliflozin ameliorates renal oxidative stress and inflammation by stimulating AMPK-Akt-eNOS pathway in the isoprenaline-induced oxidative stress model [J].
Hasan, Raquibul ;
Lasker, Shoumen ;
Hasan, Ahasanul ;
Zerin, Farzana ;
Zamila, Mushfera ;
Parvez, Faisal ;
Rahman, Md Mizanur ;
Khan, Ferdous ;
Subhan, Nusrat ;
Alam, Md Ashraful .
SCIENTIFIC REPORTS, 2020, 10 (01)
12345