Pathogenesis of dilated cardiomyopathy and heart failure: insights from cell morphology and biology.

The cause of dilated cardiomyopathy is not yet clear but the recent discovery of a chromosomal aberration as well as the presence of autoantibodies indicate a multicausal origin. Knowledge of pathogenetic mechanisms continues to evolve and includes decreased sarcoplasmic reticulum Ca2+ uptake, reduced beta-receptor density and decreased contractility, the presence of enlarged myocytes showing numerous degenerative alterations, and fibrosis. Defects in titin, a large sarcomeric protein, may be responsible for disturbances of sarcomerogenesis in dilated cardiomyopathy. New animal models are promising but significant progress will also be made using cell culture systems like adult cardiac myocytes.