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ShareSep. 10, 1999 — CHICAGO --- Caspases are a remarkable and intricately regulated network of enzymes that can trigger cell suicide in animals from yeast and worms to humans. Caspases are known to mediate programmed cell death in a number of diseases, including ischemic brain injury, or stroke.
Now, experiments conducted by researchers at Northwestern University Medical School have found that the cardiac cell death that occurs during heart "attack" is caused by activation of several caspases. In addition, they showed in a laboratory model that administering an experimental caspase inhibitor known as YVAD-cmk not only blocks this biochemical cascade but also protects heart tissue, dramatically reducing the amount of myocardial death by over 30 percent.
Vincent L. Cryns, M.D., and colleagues in the Feinberg Cardiovascular Research Institute at Northwestern published the results of a study on programmed cell death and heart attack in the September issue of the Journal of Molecular and Cell Cardiology.
"We believe that caspases may be important therapeutic targets in heart attack," said Cryns, an assistant professor at the Medical School.
Caspases are the universal effectors of programmed cell death, or apoptosis. In response to apoptotic stimuli, such as DNA damage, growth factor deprivation and stress, caspases chop up certain cell proteins and also sequentially activate other caspases down the line to follow suit, thus transmitting and amplifying death signals to cells.
The Northwestern study is the first to find that multiple caspases are activated during myocardial ischemia -- reduced oxygen flow to the heart that can lead to a heart attack.
Apoptosis is a genetically regulated response that plays an important role in development, tissue maintenance and human disease. On the one hand, programmed cell death removes cells that are no longer needed during embryonic development, e.g., the formation of individual fingers and toes from budding limbs. On the other, it also is the means by which the body eliminates damaged or diseased cells.
However, uncontrolled apoptosis causes many human illnesses, including heart disease, cancer, neurodegenerative diseases and autoimmune disorders.
Cryns' research is aimed at understanding and describing the apoptotic pathways -- the crucial steps that activate the caspase cascade and how to block them to prevent cell death associated with heart attack, stroke or other debilitating diseases.
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