Abstract
ABSTRACTSystemic autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) show significant heart involvement and cardiovascular morbidity, which can be due to systemically increased levels of inflammation or direct autoreactivity targeting cardiac tissue. Despite high clinical relevance, cardiac damage secondary to systemic autoimmunity lacks inducible rodent models. Here, we characterise immune-mediated cardiac tissue damage in a new model of SLE induced by topical application of the Toll-like receptor 7/8 (TLR7/8) agonist Resiquimod. We observe a cardiac phenotype reminiscent of autoimmune-mediated dilated cardiomyopathy, and identify auto-antibodies as major contributors to cardiac tissue damage. Resiquimod-induced heart disease is a highly relevant mouse model for mechanistic and therapeutic studies aiming to protect the heart during autoimmunity.
Highlights
The immune system is crucially involved in the maintenance of tissue homeostasis and the response to tissue damage
Resiquimod-induced systemic autoimmunity causes left ventricular dilation and affects heart function A recombinant inbred mouse line derived from C57BL/6J, FVB/NJ and NOD/ShiLtJ parental lines was treated with Resiquimod to induce systemic autoimmunity
To determine if the Resiquimod model was suitable to investigate cardiac involvement in systemic autoimmune disease, cardiac function upon treatment was measured by echocardiography and magnetic resonance imaging (MRI; Fig. 1)
Summary
The immune system is crucially involved in the maintenance of tissue homeostasis and the response to tissue damage. When it is activated by self-antigens, the immune system causes tissue damage itself and leads to autoimmune disease. Autoimmune and cardiovascular diseases are generally considered to affect distinct demographic groups. Autoimmune patients have a substantially increased risk of developing cardiovascular complications, as well as a significantly worse prognosis after myocardial infarct compared with the general population (McCoy et al, 2013). Pharmacological treatment of autoimmune patients naturally focuses on the management of the autoimmune condition; the major cause of death in autoimmune patients is related to cardiovascular problems (Jastrzebska et al, 2013). Involvement of the cardiovascular system in systemic autoimmune
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