Prevention of autoimmune myocarditis by angiotensin inhibition (164.13)

Abstract

Abstract Myocarditis, inflammation of the heart, is one of many cardiac pathologic states that can ultimately lead to heart failure. A variety of infectious and noninfectious agents can cause myocarditis, and certain individuals will develop autoimmune responses to various cardiac antigens. To study the autoimmune aspects of the disease, an animal model of experimental autoimmune myocarditis (EAM) has been developed in which immunization of susceptible mouse strains with cardiac myosin induces cardiac inflammation, hypertrophy, and fibrosis through mechanisms dependent on CD4+ T cells. We tested the ability of the antifibrotic, angiotensin-converting enzyme (ACE) inhibitor captopril to inhibit the massive fibrosis that develops during EAM. To our initial surprise, not only did captopril prevent fibrosis, but also it prevented inflammation primarily. Captopril treatment did not appear to directly affect T cell function, since T cells from captopril-treated mice proliferated and secreted proinflammatory cytokines. However, preliminary data indicate that immune cells from spleens of captopril-treated mice show reduced ability to transmigrate across endothelium ex vivo, suggesting that ACE inhibition somehow affects cell trafficking into the myocardium. Current studies are underway to further elucidate the mechanisms by which ACE inhibition mediates these effects with respect to how ACE and ACE products provide proinflammatory signals during EAM.