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Alterations in cardiac function and gene expression during autoimmune myocarditis in mice
1Center for Anesthesiology Research, The Cleveland Clinic Foundation, Cleveland, OH, 44195, USA.
Journal of Molecular and Cellular Cardiology
|October 21, 2000
Summary
Autoimmune heart inflammation (myocarditis) in mice led to cardiac dysfunction and fibrosis. This progression mimicked key features of human heart failure, establishing a link between inflammation and heart disease.
Area of Science:
- Cardiovascular Science
- Immunology
- Pathology
Background:
- Myocarditis is linked to heart failure pathogenesis.
- The precise relationship between myocardial inflammation, cardiac dysfunction, and gene expression changes remains unclear.
Purpose of the Study:
- To investigate if autoimmune-induced myocardial inflammation and fibrosis progress to cardiac dysfunction.
- To determine if this progression leads to a heart failure phenotype.
Main Methods:
- SWXJ mice were immunized with cardiac myosin to induce autoimmune myocarditis.
- Cardiac function was assessed using cardiac catheterization.
- Heart tissues were analyzed for inflammation, fibrosis, and myocyte gene expression via histology and Northern blot.
Main Results:
- Mice with myocarditis showed increased heart weight/body weight ratio from day 14.
- Cardiac function declined from day 21, accompanied by significant fibrosis.
- Gene expression analysis revealed increased atrial naturietic factor and decreased myosin heavy chain alpha starting day 21.
Conclusions:
- Autoimmune heart inflammation causes significant cardiac dysfunction.
- The observed dysfunction and phenotypic alterations resemble human and animal models of heart failure.
- This study establishes a link between autoimmune myocarditis and the development of heart failure.