1. Academic Validation
  2. SGLT2 inhibitor, canagliflozin, ameliorates cardiac inflammation in experimental autoimmune myocarditis

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

  • Int Immunopharmacol. 2022 Sep;110:109024. doi: 10.1016/j.intimp.2022.109024.
Qi Long 1 Lixia Li 2 Hongmin Yang 2 Yang Lu 2 Han Yang 2 Yaoxi Zhu 2 Yaohan Tang 2 Changhu Liu 2 Jing Yuan 3
Affiliations

Affiliations

  • 1 Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: iriszi@163.com.
  • 2 Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 3 Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: yhelen13@163.com.
Abstract

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 α-myosin-heavy chain Peptides. The expressions of NLRP3 inflammasome complexes (NLRP3, ASC, and Caspase-1) and their downstream molecules (IL-1β, 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.

Keywords

Apoptosis; Canagliflozin; Myocarditis; NLRP3 inflammasome; SGLT2i; Th17 cell differentiation.

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