Indian Researcher Has Identified Key Enzyme’s Role in Reducing Heart Disease

by Medindia Content Team on Oct 25 2007 6:35 PM

A research team led by an Indian researcher has identified a key enzyme’s role in reducing heart disease which could pave way for new target therapies to reduce plaques in the arteries.

It is due to the formation of plaques in the coronary artery, which supplies blood to the heart, that heart diseases develop.

Plaques form when monocytes, which are cells from the blood, enter the wall of the artery and consume large amounts of the ‘bad’ cholesterol, or LDL. The monocytes then become artery-clogging foam cells.

For foam cells to get rid of their cholesterol is to by making it available to HDL, or ‘good’ cholesterol, for removal.

Cholesteryl ester hydrolase (CEH), a key enzyme present in the foam cells regulates the amount of cholesterol that can be removed by HDL.

A macrophage foam cell contained fat droplets that are surrounded by CEH showing how the enzyme associates itself with fat and releases cholesterol to be picked up by HDL.

The study led by Shobha Ghosh, Ph.D., an associate professor of internal medicine, researchers at the pulmonary division in the VCU School of Medicine examined, for the first time, how cells in the artery wall make cholesterol available for removal by HDL.

In the research transgenic mice were used which were fed a high fat and cholesterol-rich diet. Because of this, the team was able to show that by increasing the removal of cholesterol from the artery clogging foam cells, the mice with the human gene for CEH developed significantly less heart disease.

“Currently the emphasis for managing heart disease is on reducing the ‘bad’ cholesterol or LDL in the circulation. Our study demonstrates that if you can increase the removal of cholesterol from the plaques, even without changing the LDL levels, there is still a significant reduction in the plaques,” Ghosh said.

"These findings not only change the current thinking of managing heart disease but also clearly open avenues for the development of new therapies,” she said.

“By identifying CEH as a new therapeutic target, we expect that in the future patients with heart disease will have more options to aggressively treat heart disease. In addition, by determining the levels of CEH in human blood cells, we hope to be able to predict susceptibility to heart disease in the future," she added.

The finding may also help in predicting a patient’s susceptibility to heart disease.

Ghosh said that in the study the efforts were on the examination of macrophage foam cells, which are responsible for storing large amounts of cholesterol and lead to the clogging of the arteries by forming plaques.

The study is published in the Journal of Clinical Investigation.