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Research findings link post-heart attack biological events that provide cardioprotection

DALLAS, March 13, 2014 Heart attack and stroke are among the most serious threats to health. But novel research at UT Southwestern Medical Center has linked two major biological processes that occur at the onset of these traumatic events and, ultimately, can lead to protection for the heart.

On one end of the cascade is the so-called Unfolded Protein Response (UPR), and at the other end are numerous proteins with modified glucose molecules attached to them. For years, researchers have made countless observations relating to these opposite ends of the spectrum. Now, researchers at UT Southwestern have discovered a pathway that links these two disparate biological occurrences, which could open the door for new types of treatment.

"Our findings uncover the direct coupling of these two important pathways and raise the prospect of therapeutic manipulation of the UPR to lessen the damage caused by heart attack and stroke," said Dr. Joseph A. Hill, Professor of Internal Medicine and Molecular Biology, and senior author of the study published in the March 13 issue of Cell.

The work by Dr. Hill's team uncovers a previously unrecognized progression following ischemia (when a tissue is deprived of oxygen and nutrients) and reperfusion (when that supply is restored, either spontaneously or therapeutically). Ischemia/reperfusion injury underlies health issues such as heart attack, stroke, and numerous other ailments including diseases of the kidney, liver, skeletal muscles, and more.

When someone suffers a heart attack, it triggers the process of the UPR inside myocytes (heart cells). A link between ischemia/reperfusion and UPR has been suggested previously, but compelling evidence was absent until the Cell study emerged.

Of the three pathways activated within the UPR, the new work implicates IRE1, which produces a molecule called spliced X-box bi

Contact: Lisa Warshaw
UT Southwestern Medical Center

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