ABSTRACT
One of the major conceptual advances in our understanding of the pathogenesis of heart failure has been the insight that it may progress as the result of the sustained overexpression of biologically active molecules, such as norepinephrine and angiotensin II. By virtue of their deleterious effects, these factors are sufficient to contribute to disease progression by provoking worsening left ventricular (LV) remodeling and progressive LV dysfunction. The term “cytokine” is applied to a group of relatively small molecular weight protein molecules that are secreted by cells in response to a variety of inducing stimuli. The first suggestion that inflammatory mediators played a role in LV remodeling was from a study in which human volunteers were administered endotoxin intravenously. The role of inflammatory mediators and programmed cell death has been examined in several studies. As an example, IL-1ß–induced activation of nitric oxide has been implicated as a mediator of programmed cell death in neonatal cardiac myocytes.
