US researchers have identified a protein which may be useful in repairing heart damage caused by a heart attack and may reduce damage during bypass surgery.
In today’s issue of the journal Science, researchers led by Daria Mochly-Rosen of Stanford University Medical Center in California report they found a compound that increases the activity of ALDH2 enzyme. The ALDH2 enzyme was found to play a role in protecting the heart from damage, said Daria Mochly-Rosen, a professor of chemical and systems biology at Stanford, and lead author of the study.
The molecule which activates the enzyme called aldehyde dehydrogenase 2 (ALDH2) is called Alda-1. ALDH2 is usually involved in breaking down alcohol in the body. The newly discovered compound, Alda-1, was able to keep enzyme levels high during nitroglycerin treatment which reduces the amount of damage caused by the drug. Nitroglycerine treatment is given to patients with chest pain to widen arteries and improve blood flow. ALDH2 helps the drug convert into its active form, but prolonged use of the nitroglycerin can reduce the presence of the enzyme, which may lead to heart damage. The enzyme gets rid of toxins that accumulate when the heart is not getting enough oxygen and nutrients.
"Although this enzyme was discovered a long time ago, my research group knew nothing about it except that it helps remove alcohol when people drink," said study leader Dr Daria Mochly-Rosen.
In animal studies led by Mochly-Rosen, rats resistant to heart muscle damage caused by lack of oxygen had higher levels of the ALDH2 enzyme. The enzyme reduces the tissue damage done by free radicals, which attack the nearest stable molecule, trying to capture an electron to gain stability. When the "attacked" molecule loses its electron, it becomes a free radical itself, beginning a chain reaction. If the free-radical production becomes excessive, damage can occur.
However, it will take many years before this could be confirmed in humans, but if the theory fulfills its promise, the newly discovered compound could be given to in a situation where the heart is the victim of free radical damage. Researchers also hope that future studies will demonstrate that Alda-1 can be given to patients in order to prevent such damage.
The researchers plan to explore how the process works in other animals. "We need to make it more potent, so it binds better and has the same effect at lower concentrations, because with any drug, we always like to give the lowest dose possible," said Hurley, director of the Center for Structural Biology at the Indiana University School of Medicine.
The findings could prove helpful for those patients who do not appear to respond to nitroglycerin, said Henry Weiner, a professor of biochemistry at Purdue University. A drug like Alda-1 may also be able to help people with conditions involving so-called oxidative stress Alzheimer's and Parkinson's disease, Mochly-Rosen said.
The drug may also be useful for those people who suffer from angina the chest pain that occurs when the heart muscle does not get enough oxygen-rich blood. More research is needed in order to understand if the drug could be given to patients after they suffer a stroke to minimize the heart damage.
