The Amino Acid Which Holds the Key to Cardiac Health

What's the difference between suffering a heart attack and being protected from such a vascular incident? According to Michigan University researchers, a single amino acid.

They suggest the amino acid histidine could become the key for new cardiovascular disease therapy.

In a study to be published January 22 in Nature Medicine, U-M scientists describe how they created a modified form of a heart muscle protein called troponin I and how it improved cardiac function in mice and in damaged human heart cells.

The secret was using genetic engineering technology to replace one amino acid called alanine, found in the adult form of troponin I, with a histidine from the fetal form of the same protein.

"The most important finding of our study was that this modified troponin I protein dramatically improved heart function under a variety of conditions associated with cardiovascular damage and heart failure," says Sharlene Day, M.D., co-first author of the paper.

"This study provides the first evidence that a single histidine substitution in troponin I can improve short and long-term cardiac function in laboratory mice with heart failure. The fact that we also were able to rescue the functionality of damaged human heart cells is a significant advance," says Joseph M. Metzger, a U-M Medical School.

Troponin I is an important cardiac muscle regulatory protein that controls the calcium sensitivity of heart muscle cells. The ability to respond to calcium is important, because it's what causes the heart to contract efficiently and pump blood through the body. When blood flow to the heart is compromised, such as during a heart attack, acid accumulates in cardiac cells - a condition called acidosis. This causes cells to become less responsive to calcium, which can lead ultimately to heart damage and cardiac failure.

During embryonic development, the fetal form of troponin I is present in the fetal heart, which makes it more resistant than the adult heart to the harmful effects of acidosis and low oxygen that can occur during pregnancy or delivery.