[Signal transduction in heart failure].

Heart failure is the final culmination of protracted disease status precipitated by underlying ischemic disease, valvular insufficiency and viral myocarditis. The factors that lead to the development of heart failure are still not fully understood. In mammalian cells, four parallel kinase cascades have been described that finally lead to the activation of members of the mitogen-activated protein kinase(MAPK) family, such as ERKs (p42 and p44), JNK and p38 protein kinase. Apoptosis signal-regulating kinase 1 (ASK1), an upstream activator of JNK and p38, was shown to promote heart dysfunction and dilation as well as cardiac fibrosis. Meanwhile, not only myocyte apoptosis but also myocardial interstitial changes such as extracellular matrix deposition, activation of fibroblasts, and narrowing of vessel lumens play important roles for the progression of heart failure.