Cardiologist finds way to boost body’s natural defenses to damage from heart attack
Steven P. Jones, Ph.D., an assistant professor of medicine at UofL, said his team’s findings could open the door for the development of new treatments for patients who have suffered heart attacks or have chronic heart failure.
A sugar that occurs naturally in the body appears to play a major role in protecting cardiac tissue from damage during a heart attack, and that protective benefit can easily be augmented with drugs, according to study by a team of researchers at U of L and Johns Hopkins that appears in the March 4 issue of Circulation, the Journal of the American Heart Association.
The study, conducted on laboratory mice and isolated tissue samples, found that the number of heart cells damaged by oxygen deprivation following an actual or simulated heart attack was reduced by up to 35 percent if researchers augmented the amount of the sugar present in the body, said Steven P. Jones, Ph.D., the study’s principal investigator and an assistant professor of medicine at UofL’s Institute of Molecular Cardiology.
The team also discovered that the sugar, N-acetylglucosamine, becomes attached to at least one specific protein in cardiac muscle cells, although the exact sequence of events remains unclear.
“We now know that this sugar is added to proteins, and that confers protection to the heart during a heart attack,” Jones said. “We also have identified a particular protein that is present in the mitochondria of heart muscle that is involved in this process. Mitochondria make energy for the cells, and we think the addition of the sugar to that protein helps the mitochondria withstand damage from heart attacks. If we can protect the mitochondria, we can ultimately protect the heart at large.
“What we don’t fully understand are the molecular mechanisms involved. This appears to be a cellular response to stress preceding an ischemic event, in which blood flow to healthy tissue is cut off, as happens during a heart attack. We think this process is a way for the cells to set off an alarm, and say, ‘Batten down the hatches — something bad is going to happen’.”
The scientists conducted the study by inducing or simulating heart attacks in one group of mice and tissue samples, then measuring the amount of dead heart tissue. Another group was given a compound called PUGNAc, which boosts the levels of N-acetylglucosamine on proteins, and was then subjected to the same scenarios. The latter group fared much better, with 25 to 30 percent less damage to heart muscle, Jones said.
“The biology that’s at work in the heart here is completely unknown, so it’s much too early to talk about studying this approach in people,” he added. “But if we can understand this biology better, we may be able to explain the basic processes by which metabolic signaling occurs in the heart, and that knowledge could open the door for the development of treatments for patients who have suffered a heart attack or who have chronic heart failure.”
The study was conducted with grant funding from the National Institutes of Health and the American Heart Association.
