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

Area of Science:

• Cardiovascular Medicine
• Immunology
• Pharmacology

Background:

• Myocarditis is an inflammatory heart condition linked to dilated cardiomyopathy and heart failure.
• Canagliflozin (CANA), known for its glucose-lowering effects, also shows anti-inflammatory and cardioprotective properties in heart failure.
• The therapeutic potential of CANA in myocarditis remains largely unexplored.

Purpose of the Study:

• To investigate the efficacy of Canagliflozin (CANA) in treating experimental autoimmune myocarditis (EAM).
• To elucidate the underlying mechanisms of CANA's action in mitigating cardiac inflammation and dysfunction.

Main Methods:

• Experimental autoimmune myocarditis (EAM) was induced in mice using α-myosin-heavy chain peptides.
• Mice were treated with Canagliflozin (CANA).
• Cardiac function, inflammation markers (NLRP3 inflammasome, IL-1β, IL-18, Th17 cells), and apoptosis (Bax/Bcl-2 ratio, Cleaved Caspase-3, TUNEL assay) were assessed.

Main Results:

• CANA treatment significantly reduced cardiac inflammation and improved cardiac function in EAM mice.
• Expressions of NLRP3 inflammasome components and downstream cytokines (IL-1β, IL-18) were downregulated by CANA.
• CANA decreased Th17 cell infiltration, reduced apoptosis markers, and improved the Bax/Bcl-2 ratio in the heart.

Conclusions:

• Canagliflozin (CANA) demonstrates significant anti-inflammatory and cardioprotective effects in experimental autoimmune myocarditis.
• CANA ameliorates cardiac inflammation and apoptosis, suggesting its potential as a therapeutic agent for myocarditis.