![]() ![]() Pathologic growth of the myocardium can induce concentric remodeling of the ventricle that results in myocyte growth in a cross-sectional area, such as with hypertension or from hypertrophic cardiomyopathy due to mutations in sarcomeric genes (Figure 1). The hypertrophic growth of the myocardium is typically initiated by signal transduction pathways in response to either neuroendocrine factors or an ill-defined mechanical stretch– or wall tension–sensing apparatus ( 6– 10). Pathologic hypertrophy of the myocardium temporarily preserves pump function and reduces ventricular wall stress, but prolonged cardiac hypertrophy is a leading predictor for arrhythmias and sudden death as well as dilated cardiomyopathy and heart failure ( 2– 5). When contractile performance is perturbed or reduced in response to diverse (patho-)physiologic stimuli, the heart typically remodels and hypertrophies, in association with increases in myocyte cell volume ( 1). The primary function of the heart is to contract and pump blood. Cardiac hypertrophy and clinical considerations We focus our discussion on selected therapeutic targets that have more recently emerged and have a tangible translational potential given the available pharmacologic agents that could be readily evaluated in human clinical trials. The majority of these are based on intracellular signaling pathways considered central to pathologic cardiac remodeling and hypertrophy, which then leads to heart failure. Here we discuss therapeutic avenues emerging from molecular and genetic studies of cardiovascular disease in animal models. Cardiac hypertrophy is the strongest predictor for the development of heart failure, arrhythmia, and sudden death. Initially, such cardiac hypertrophic growth is often compensatory, but as time progresses these changes become maladaptive. The heart responds to many cardiopathological conditions with hypertrophic growth by enlarging individual myocytes to augment cardiac pump function and decrease ventricular wall tension. Cardiovascular disease is the number one cause of mortality in the Western world. ![]()
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