Harvard Docs See Cure For Broken Hearts

The good news: Harvard Medical School researchers have identified an enzyme inhibitor and growth factor that, in combination, appear able to erase some of the damage from heart attacks.

The bad news: the enzyme inhibitor is a known toxin to humans.

The researchers’ discovery—which suggests that the loss of cardiac function and accompanying tissue scarring caused by a heart attack may be reversible—will be published in the Oct. 17 issue of the Proceedings of the National Academy of Sciences.

A Harvard professor of cell biology and pediatrics, Mark T. Keating, and an instructor in pediatrics at the Harvard-affiliated Children’s Hospital, Felix Engel, administered two drugs to rats who had suffered induced heart attacks. One of the drugs targets p38 MAP kinase, an enzyme that prevents heart muscle cells from undergoing cellular division. The other is FGF1, a growth factor that promotes the creation of new blood vessels.

The researchers found that rats who had received the two drugs experienced significant improvements in heart function and a reduction in the amount of scar tissue, which inhibits pumping capacity.

Only those rats receiving both the enzyme inhibitor and FGF1 showed significant improvements in both the proliferation of heart cells and heart function. Though the administration of only the inhibitor did result in the creation of new heart muscle cells, it did not improve cardiac function. The rats that only received the growth factor did not show as much cell proliferation as those receiving the inhibitor.

Heart muscle cells, or cardiomyocytes, “need a blood supply and oxygen to survive,” said Engel. “FGF1 did not have a great effect on cell proliferation, but we found it was providing a new blood supply. If you just inhibit p38 MAP kinase, you don’t get blood vessels.”

But there are still some major obstacles in using these drugs on humans to reverse cardiac damage. Since the p38 MAP kinase inhibitor is a known toxin to humans, a different nontoxic small molecule with a similar function must be used.

Engel said the drugs were administered to the rats directly after the heart attack, so future work will concentrate on whether or not this combination of drugs can repair older damage to the heart.