Polyamine metabolism and the hypertrophic heart.

Cardiac muscle hypertrophy is one of the most important compensatory responses of the heart to multiple stresses that may be placed on it. If the stress is not relieved, sustained hypertrophy may progress to dysfunction and heart failure. The polyamines putrescine, spermidine, and spermine increase within hours of various types of experimentally induced cardiac hypertrophy, along with ornithine decarboxylase (ODC) gene expression. Several animal models have implicated ODC induction as an important factor in the development of hypertrophy, particularly in response to β-adrenergic stimulation. Novel transgenic mouse lines that overexpress several enzymes of polyamine metabolism in the heart have been generated in recent years, and crosses of these lines have pointed to decarboxylated adenosylmethionine and its control by S-adenosylmethionine decarboxylase as another important element in maintaining cardiac polyamine homeostasis. The activity of arginase is thought to play a regulatory role in the biosynthesis of both nitric oxide (NO) and polyamines, and NO deficiency has been linked to the development of cardiac hypertrophy. Genetically altered mouse lines with changes in arginine and NO metabolism in the heart are available, many of which possess cardiac abnormalities. These models will provide a valuable means to address the interdependence of arginine and ornithine metabolism in the development of myocardial hypertrophy and failure. Use of these tools may lead to a better understanding of the control of the signaling pathways that include the polyamines, arginine, and NO, allowing future work to focus on the interactions between these pathways in the development of heart disease.