Is Nuclear Factor κB an Attractive Therapeutic Target for Treating Cardiac Hypertrophy?

ardiovascular disease is the leading cause of morbidity and mortality in the United States. In most instances, heart failure is the final consequence of many underlying disease etiologies such as long-standing hypertension, coronary heart disease, valvular insufficiency, arrhythmia, viral myocarditis, and mutations in sarcomereencoding genes. A compensatory enlargement of the myocardium, or hypertrophy, typically accompanies many of the predisposing insults discussed above and is a leading predictor for the development of more serious and life-threatening disease. Given the strong association between the presentation of pathological cardiac hypertrophy and a progressive deterioration in myocardial function, investigators have focused on understanding the molecular mechanisms that initiate the compensatory growth response or that precipitate the transition to heart failure. A number of signal transduction pathways are thought to play pivotal roles in mediating the hypertrophic growth of the myocardium in response to pathological stimuli. In this issue of Circulation, Cook et al 4 focus their attention on the nuclear factor (NF)-B signaling pathway as a potentially important intracellular mediator of cardiac hypertrophy.