One More Step Towards Cardiac Regeneration

A scientific study of the interconnections between three molecules that control fetal, heart-muscle-cell proliferation in a mouse model, carried out by a team of researchers at the University of Pennsylvania School of Medicine, can help cardiologists better understand the natural repair system of the heart, after a cardiac event, and also show them how to use cardiac stem cells for regenerative therapy.

In a normal, adult heart, the cells of the muscle do not replicate in adult tissue, instead they multiply with those abandoned during development, and this is one reason for which people who have experienced a heart attack are unable to grow enough heart muscles to compensate for the loss.

The experiment carried out by the researchers proved that an enzyme called Hdac2 had a direct impact on a protein called Gata4, and a third protein called Hopx, this last adopting a new function.

The Hopx protein belong s to an ancient family of conserved proteins that normally bind DNA, except that in this case, instead of binding DNA, it brings the other two proteins – Hdac2 and Gata4, together, and by doing so, Hopx controls the rate of heart muscle cells division.

Team leader Jonathan Epstein, MD, chair of the Department of Cell and Developmental Biology said that “although the degree to which hearts can repair themselves after injury is controversial, if there is a natural regeneration process, even if normally insufficient and modest, then approaches leveraging this insight this could be useful for boosting new growth so that it has a clinically significant effect.”

“We are eager to see if drugs like Hdac inhibitors will have this effect,” he added.

Another unexpected finding concerned the Hdac2 protein, which normally acts like a switch that controls the way that DNA is organized inside the cell, thus turning on and off large groups of genes.

Currently, Hdac inhibitors are already in trials for cancer and one in particular – valproic acid, has been treating seizures for decades now.

Jonathan Epstein worked with Chinmay Trivedi, MD, PhD, an Instructor in the Department of Cell and Developmental Biology, and the findings were reported in the cover article of the latest issue of Developmental Cell.