Caspase Inhibition May Retard Dilated Cardiomyopathy

Dilated cardiomyopathy (DCM) is a condition wherein a failing heart significantly increases its size in an effort to meet the metabolic needs of the body. While this is not a rare cardiovascular pathology by any measure, much of the mechanisms which govern this phenomenon are still not well understood. To date, there is no known therapy which is guaranteed revert a dilated myocardium to its normal size. A leading hypothesis, however, is that the cardiomyocytes of a myopathic myocardium will undergo cell apoptosis, which ultimately promotes ventricular failure (see SNBAL-2, “Controversies in Ventricular Remodelling”). If this hypothesis is supported, an obvious therapy for patients suffering from DCM would involve the inhibition of cell apoptosis.

Research published in a 2003 edition of Circulation suggests that such inhibition may well be possible. One of the chief caspases—enzymes involved in cell apoptosis—in the mouse-model of dilated cardiomyopathy has been identified in pregnant mice (pregnant mice are particularly helpful in the study of DCM because the normal volume/pressure overloading characteristics that they experience due to pregnancy roughly model the overloading characteristics present in DCM). The inhibition of this caspase has important implications for the cell apoptosis allegedly responsible for DCM:

“Caspase inhibitors may block and possibly reverse the death program. Caspase inhibitors may also inhibit the cleavage of multiple intramyocyte substrates, including sarcomeric components, degradation of which may cause contractile dysfunction.”

Their research has already shown caspase inhibitors to be effective in blocking cell apoptosis (and thereby blocking heart failure) in pregnant mice. If this model carries over into human physiology, these findings could be hope for the many sufferers of this fatal disease.

For more information, see the referenced Circulation article from the American Heart Association, Inc. .