Changes in calcium cycling precede cardiac dysfunction during autoimmune myocarditis in mice

Area of Science:

• Cardiology
• Molecular Biology
• Immunology

Background:

• Myocardial inflammation is a key factor in dilated cardiomyopathy and other cardiac conditions.
• Previous studies demonstrated reduced left ventricular function in mice experiencing autoimmune myocarditis.

Purpose of the Study:

• To investigate if impaired cardiac function in autoimmune myocarditis is due to alterations in contractility and calcium (Ca2+) cycling.
• To analyze changes in cardiac myocyte function and protein expression at different disease stages.

Main Methods:

• Cardiac myocytes were isolated from mice with myocarditis and controls at day 18 (pre-dysfunction) and day 35 (during dysfunction).
• Cell shortening and Ca2+ transients were measured.
• Protein levels regulating contractility and intracellular Ca2+ ([Ca2+](i)) were quantified using Western blot analysis.

Main Results:

• No changes in cell shortening or systolic Ca2+ were observed on day 18, despite reduced diastolic Ca2+.
• By day 35, reduced cell shortening and systolic Ca2+ transients correlated with decreased diastolic Ca2+.
• Significant reductions in phospholamban and sodium/calcium exchanger protein levels were noted in affected mice at both time points. Calsequestrin was reduced by day 35.

Conclusions:

• Decreased diastolic Ca2+ and reduced levels of phospholamban and sodium/calcium exchanger proteins may drive disease progression in autoimmune myocarditis.
• Altered calsequestrin levels might be linked to the observed systolic dysfunction in this model.