Foetal clue to adult heart damage


Feb 19, 2007

Scientists have found the key to why a mechanism designed to help build foetal hearts starts up again when adults are in the early stages of heart failure.

US researchers say it appears triggers such as high blood pressure set off this system, which should be dormant.

Writing in Nature Medicine, they say they have found a way of "hitting the off switch" in the system, offering hope for new drug treatments.

British experts said the study was an "important discovery".

It was already known that, in almost all forms of heart failure, the heart begins to express genes that are normally only expressed in the foetal heart - but no-one knew why.

The team, at the University of Pennsylvania School of Medicine, found that an enzyme called HDAC which is important in foetal heart-cell development.

HDAC is a "switch" that regulates how DNA is packaged inside the cell and how large groups of related genes are turned on and off.

Old programmes 'reactivation'

During an embryo's development, HDAC regulates proliferation of heart cells in the embryo.

It appears that, when it is "switched on" again in a failing adult heart, it makes existing heart cells bigger because the organ cannot make new cells easily.

This enlargement of heart cells, known as cardiac hypertrophy, is a precursor to many forms of congestive heart failure (CHF).

By preventing the action of the enzyme in adult mice, it was found that the foetal-gene programme can be prevented from restarting.

Dr Jonathan Epstein said: "We found that in various mouse models of cardiac hypertrophy and heart failure, treatment with chemical HDAC inhibitors prevented the beginning of the downward slide to progressive heart failure."

"It's as if old programmes are being reactivated in a sick heart.

HDAC inhibitors are already being tested, because the enzyme can malfunction in a number of other ways, including potentially fuelling cancer growth.

One, valproic acid, is already is use to treat seizures.

Judy O'Sullivan, a spokesperson for the British Heart Foundation, said: "This is an important discovery that may one day impact on the treatment of enlarged hearts and heart failure.

"It is far too early to predict when, if ever, this will lead to a benefit for people with heart failure, but we look forward to seeing how research progresses in this field."