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Research findings link post-heart attack biological events that provide cardioprotection
Date:3/13/2014

nding protein 1 (Xbp1s), as a direct activator of the hexosamine biosynthetic pathway (HBP). The HBP is responsible for producing modified glucose molecules that couple to numerous proteins, leading to beneficial changes in their function, stability, and location within the cell. This coupling, termed O-GlcNAcylation, has favorable effects on disease-injured cells, including myocytes.

Previously, researchers have verified that the O-GlcNAcylation process provides ample protection for the heart, in addition to many other cell types and tissues. However, what activated the O-GlcNAcylation process was unknown, until now.

"We discovered a linear cascade downstream of ischemia/reperfusion that involves UPR activation, elicitation of Xbp1s, consequent activation of the HBP, and robust cardioprotection," said Dr. Hill, also the Chief of the Division of Cardiology and Director of the Harry S. Moss Heart Center. "It is the first time that researchers have been able to unveil a clear pathway leading to significant cardioprotection, often thought of as the 'holy grail' of cardiology."

While it is clear that the O-GlcNAcylation process protects the heart, we still do not understand how protection is mediated, notes Dr. Hill.

"However, now we know what turns the process on, a finding that points the way to future research and possibly new therapeutic means by which to safeguard the heart," he said.

The study, undertaken by Dr. Zhao Wang, postdoctoral research fellow and first author of the paper, directly raises the question of whether Xbp1s can be manipulated therapeutically. If the body is able to produce more Xbp1s, then doing so would enhance the heart's ability to withstand a heart attack. In fact, using mice engineered to have extra copies of Xbp1s in the heart, Dr. Wang initiated heart attacks that were ultimately smaller and less harmful to the host. Conversely, when he deleted the gene altogether and initiated heart attacks
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Contact: Lisa Warshaw
lisa.warshaw@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
Source:Eurekalert  

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