Experimental Heart Failure Models of Cytokine Overexpression

Abstract

Heart failure secondary to systolic dysfunction is a progressive cardiovascular disease that affects over 5 million people in the U.S. While the initial cause of heart failure in most patients is myocardial damage, the heart usually accommodates to the damage. However, over time, the heart remodels with the development of cardiac dilatation, cellular hypertrophy, cell slippage, diminished adrenergic responsiveness, apoptosis and extracellular matrix fibrosis and restructuring. Over the past decade, there has been a substantive increase in our knowledge of the pathobiology of the development of the heart failure phenotype. This increased knowledge has in part been attributable to advances in the sciences of cell and molecular biology and their application to studies of the failing human heart. However, our improved understanding of the molecular and cellular events leading to the development of heart failure and in particular the transition from compensated to de-compensated myocardial function can also be attributed to studies of new and novel animal models. Indeed, it is studies in animal models that have contributed seminal information regarding the fundamental role of the pro-inflammatory cytokines in the development of the heart failure phenotype. This Chapter will review in detail the observations from animal models that have supported the “Cytokine Hypothesis” of heart failure and will detail how animal models of cytokine over-expression have provided novel experimental platforms for evaluating the efficacy of anti-cytokine pharmacotherapy.