New method may help prevent cardiac fibrosis

By Staff
|
Google Oneindia News

Washington, April 23 : An animal study by researchers at the University of California, San Diego School of Medicine has revealed that a molecule called Epac plays a significant role in integrating the body's pro-and-anti-fibrotic response.

The researchers focussed their attention on cardiac fibrosis, which usually occurs in patients who have suffered an infection of the heart muscle or a heart attack.

Such fibrosis in turn leads to a condition known as diastolic dysfunction, wherein the heart gets so stiffened that it cannot adequately fill with blood and empty itself.

"An old heart is a stiff heart and some injured hearts are stiff as well," said Dr. Paul A. Insel, a professor of Pharmacology and Medicine who led the study.

"Much of the decrease in cardiovascular function that occurs with aging or, in some patients after a heart attack, can be explained by fibrosis. We wondered: What is responsible for excessive fibrosis" Is there a way to decrease or possibly reverse it," he added.

Previous studies have already shown that a messenger molecule inside of cells, known as cAMP, can block fibrosis in the heart.

With this information at hand, Dr. Insel and his colleagues explored the mechanism leading to the anti-fibrotic effect.

The researchers found that the Epac molecule mediates cAMP actions that are involved in cardiac fibrosis. They also discovered that Epac helps regulate other proteins that contribute to cell death, division, migration and motility.

"We found that Epac activation exerts a very important impact on the function of fibroblasts, the cells responsible for making and secreting collagen and thus for producing tissue fibrosis," he said.

"Most exciting was our discovery that multiple agents that promote fibrosis decrease the expression and activation of Epac in fibroblasts from several different tissues - not only in the heart but also in lung, liver and skin," he added.

While experimenting on rats and mice, the researchers found decreased Epac expression in regions near the site of heart attacks.

Increasing Epac expression enabled them to block the ability of agents to promote fibrosis, they said.

The researchers say that stimulation of the cAMP signalling pathway is a potential way to blunt fibrosis because increases in cAMP levels can decrease the function of fibroblasts after cell injury.

They believe that increases in Epac expression may be one way to do this, especially in cardiac fibroblasts.

They have even tested this possibility in experiments wherein they treated fibroblast cells by altering Epac expression.

"Using this strategy to overexpress Epac, we produced an anti-fibrotic effect, thereby inhibiting the synthesis of collagen. Other experiments showed that decreasing Epac expression favored fibrosis; in other words, were pro-fibrotic. Overall, the results show the central role of Epac in determining pro-fibrotic and anti-fibrotic response," said Dr. Insel.

The study has been reported in the online edition of the Proceedings of the National Academy of Science (PNAS).

ANI

For Daily Alerts
Get Instant News Updates
Enable
x
Notification Settings X
Time Settings
Done
Clear Notification X
Do you want to clear all the notifications from your inbox?
Settings X
X