Figure 1.

Progression of heart failure and the role of oxidative and nitrosative stress. The mechanisms that lead to heart failure are of multiple origins and include acute and chronic ischemic heart disease, cardiomyopathies, myocarditis and pressure overload. These diseases result in a mismatch between the load applied to the heart and the energy needed for contraction, leading to mechanoenergic uncoupling. Following initial insult, secondary mediators such as angiotensin II (Ang II), noradrenaline (NA), endothelin (ET) and pro-inflammatory cytokines [e.g. tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6)], in concert with oxidative and nitrosative stress, act directly on the myocardium or indirectly via changes in hemodynamic loading conditions to cause endothelial and myocardial dysfunction, cardiac and vascular remodeling with hypertrophy, fibrosis, cardiac dilation and myocardial necrosis, leading eventually to heart failure. The adverse remodeling and increased peripheral resistance further aggravate heart failure. Abbreviations: MMP, matrix metalloproteinase; PARP, poly(ADP-ribose) polymerase.