Pitt makes heart breakthrough

Imagine an aircraft carrier. It has a set of deliberately structured building blocks and… Imagine an aircraft carrier. It has a set of deliberately structured building blocks and supports to withstand inclement weather conditions. If those supports, however, were changed, what would happen to the overall function of the ship?

This is the same question Pitt professor Sanjeev Shroff and his team are trying to figure out with regard to heart muscle functions.

“I want to figure out how molecules, proteins and cells that make up the heart and vessels contribute to the overall cardiac and vascular function,” Shroff said.

Shroff and his team discovered a way to control heart muscle functions, specifically contractions, by manipulating two prominent enzymes in the heart muscle. Chemical modification is one of two methods to affect muscle contraction, the other being a natural change in the content of the proteins.

“It is generally nature’s way of doing certain things and regulating protein control on contractions,” Shroff said.

After studying portions of heart muscles, Shroff found that the enzymes regulating heart muscle contractions are histone acetyltransferases (HATs) and histone deacetylases (HDACs).

The process advances the research for treating heart failure diseases, creating an alternative method to boost cellular calcium content and therefore strengthening heart muscles.

Shroff used the process of acetylation – adding or removing acetyl protein groups to the muscles.

“We found the process to be very active inside and outside of the nucleus of the heart muscle,” Shroff said.

The process is extensively studied for regulating genes in the nucleus of a cell.

During acetylation, HATs and HDACs attach to the muscles, regulate the proteins and change the properties of the muscle itself. HATs facilitate the process, and HDACs inhibit the added acetyl group.

By using acetylation, Shroff wanted to find out if calcium sensitivity plays an active role in muscle contraction.

“The calcium studies how the muscle responds to various levels of calcium,” he said. “The more calcium, the more the sensitivity increases and the stronger the contraction.”

Unlike current calcium sensitivity methods, Shroff’s method does not increase the amount of calcium injected into the heart muscle but rather inhibits the level of HDACs.

“At the end of the day, they all increase calcium in the muscles and it costs a lot of energy required to consume more oxygen,” Shroff said.

Shroff first became interested in the study when his colleague from the University of Chicago sent him a slide of a stained nuclear muscle with HATs and HDACs.

“Where the proteins attached was a place known for contraction, and I wanted to know if it could change the contraction of the muscle,” he said. “There must have been a reason, it couldn’t have been random.”

The next step involves regulation in the whole body, not just in muscle samples.

“We want to understand these pathways further,” Shroff said. “Does is occur in living human organisms?”

Shroff believes that it might exist in animals but in smaller proportions, testing mice to find how significant acetylation is when working with operating processes.