Regulation of Cardiac Hypertrophy: the nuclear option

Cardiac hypertrophy is the response of the heart to an increased workload. After myocardial infarction (MI) the surviving muscle tissue has to work harder to maintain cardiac output. This sustained increase in workload leads to cardiac hypertrophy. Despite its apparent appropriateness, cardiac hypertrophy is an independent risk factor for the development of heart failure and is therefore called pathological hypertrophy. That hypertrophy is not bad per se, is illustrated by the hypertrophy that takes place after regular endurance exercise training. This so-called physiological hypertrophy is not associated with an increased risk of cardiovascular disease. We hypothesized that the changes between pathological and physiological hypertrophy are the result of genetic reprogramming early after onset of the hypertrophic stimulus. We aimed to identify the changes in an unbiased and integrative fashion in a physiologically relevant large animal model. We found that pathological and physiological hypertrophy have distinct gene expression profiles. Also the transcription factors that drive the genetic reprogramming are different. The glucocorticoid receptor was a particularly interesting transcription factor, as it is activated in pathological hypertrophy and less active in physiological hypertrophy.

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