Our data suggest that this process is defective in cystic fibrosis and may explain the presence of excessive amounts of high molecular weight DNA in the mucus of patients with the disease. We are identifying alterations in spontaneous apoptosis in mice that lack the gene for the cystic fibrosis transmembrane regulator. Myocardial ischemia results in death of cardiomyocytes through necrosis and apoptosis. We hope to determine specific biochemical events during apoptosis that can be used as targets of therapeutic intervention. In addition, using adenovirus-mediated gene transfer, we showed that the pathway is essential for death of cardiomyocytes after ischemia simulated by metabolic inhibition.
Studies are under way to identify the molecular targets.
We also showed that caspase activation is an essential step in the apoptosis of cardiomyocytes after metabolic inhibition, and we found that caspases 9 and 10 are present in cardiomyocytes. We plan to characterize the regulation of caspase activation during ischemia and reperfusion and to evaluate mitochondrial alterations. Apoptosis and cardiovascular disease. R.L. Apoptosis in myocardial ischemia-reperfusion. N. Y. Acad.