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New study in 'Nature' demonstrates protection against cell death during heart attack

CINCINNATI -- A new study, conducted at Cincinnati Children's Hospital Medical Center and published in the journal Nature, has uncovered a fundamental mechanism by which cells die a finding that could quickly lead to improved emergency treatments for heart attack and stroke.

The Cincinnati Children's researchers discovered that blocking a particular protein in mice protects the heart from injury due to loss of blood flow during a heart attack. Moreover, drugs already exist that block this protein cyclophilin D but they have never been used in actual patient care, partially because data didn't exist until now to prove they would work, according to Jeff Molkentin, Ph.D., a researcher at Cincinnati Children's and the study's senior author.

Cyclophilin D resides within the mitochondria of a cell. The mitochondria are the power plants of a cell and are responsible for the majority of energy production. When mitochondria do not function properly, such as when tissue is deprived of oxygen, cells begin to die through a process involving rupture of the mitochondria. When cyclophilin D is deleted from the mitochondria, however, a cell's ability to die is blocked, according to Dr. Molkentin.

"When a person comes to a hospital and it's realized that he or she is having a heart attack or stroke, one of the first things done is to re-establish blood flow," says Dr. Molkentin. "At this point, cells have not yet died. But when flow is re-established there is a huge burst of reactive oxygen, and that's when cells die. We hypothesize that if, at the same time you re-establish flow you infuse a cyclophilin D inhibitor, you might profoundly affect the heart or brain and, presumably, protect it."

A class of drugs already exists that blocks cyclophilin D. The most well known one is cyclosporine, a drug used to prevent rejection in organ transplantation. Cyclosporin has a downside, however. In addition to blocking cyclophilin D, it also b
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Contact: Jim Feuer
jim.feuer@cchmc.org
513-636-4656
Cincinnati Children's Hospital Medical Center
30-Mar-2005


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