The Yin/Yang of Innate Stress Responses in the Heart

The ability of the myocardium to successfully adapt tosuperimposed environmental stress, whether it resultsfrom hemodynamic overloading or myocardial ischemiaand/or infarction, ultimately determines whether the heartwill decompensate and fail, or whether instead it willmaintain preserved function. Three of the critical mechanisms that allow the heart to withstand environmentalstress are depicted in Figure 1: cardiac hypertrophy, cardiac myocyte cytoprotective responses, and cardiac repair. Despite the long-standing recognition that cardiachypertrophy, cytoprotection, and repair are critical formaintaining myocardial homeostasis, the molecules thatmediate and integrate the myocardial response to environmental stress, both at the level of the intact myocyteand for the ventricle as a whole, remain poorly understood. In this review, we focus on the emerging role thatproinflammatory cytokines play as autocrine/paracrinefactors that are responsible for initiating, integrating, andmaintaining the myocardial response to environmentalstress. The theme that emerges from this discussion is thatthe short-term expression of proinflammatory cytokinesmay provide the heart with an adaptive response to environmental injury, whereas long-term expression of thesecytokines may be frankly maladaptive by producing overtcardiac decompensation...