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Mechanisms of Inflammatory Cardiomyopathy

Rajkumar Arumugam, University of Nebraska - Lincoln


Cardiovascular diseases are the leading causes of death worldwide. Myocarditis, also termed inflammatory cardiomyopathy, is one predominant cause of heart failure in young adolescents. Individuals affected with myocarditis can develop dilated cardiomyopathy (DCM), but the underlying mechanisms remain elusive. Autoimmunity is suspected in the DCM pathogenesis by demonstrating the presence of autoantibodies for a variety of self-antigens, but their significance is unclear. Conversely, limited data are available as to the pathogenic role of antigen-specific T cells. In this research, we tested the hypothesis that cardiac reactive T cells have a role in inflammatory cardiomyopathy that can potentially be suppressed by induced regulatory T cells (iTregs). First, by using sarcoplasmic/ endoplasmic reticulum calcium ATPase 2a (SERCA2a) as a model autoantigen, we demonstrate that antigen-presenting cells from myocarditis-susceptible, naïve A/J mice constitutively express SERCA2a that can trigger T cell responses antigen-specifically. These investigations led us to identify SERCA2a as an autoantigen in the mediation of endothelial cell damage by an autoimmune reaction. Second, by establishing the T cell receptor (TCR) transgenic mice for cardiac myosin heavy chain (Myhc)-α 334-352, we noted that the TCR was common to both CD4 and CD8 T cells that permits us to determine their functionalities within a single transgenic system. Third, we have established a platform of cellular therapy to generate iTregs by encapsulating cytokines namely, interleukin-2 and transforming growth factor-β with the biodegradable poly (lactic-co-glycolic acid) nanoparticles. All of these tools are helpful to determine the functionalities of antigen-specific T cells in various experimental systems that may involve infectious or non-infectious triggers of inflammatory cardiomyopathy.

Subject Area

Immunology|Cellular biology

Recommended Citation

Arumugam, Rajkumar, "Mechanisms of Inflammatory Cardiomyopathy" (2021). ETD collection for University of Nebraska-Lincoln. AAI28718915.