It is literally very difficult to mend a broken heart. Despite its importance, the heart is notoriously bad at regenerating itself after injury. If it is damaged – say, by a heart attack – it replaces the lost muscle with scar tissue rather than fresh cells. That weakens it and increases the chance of heart failure later on in life. No wonder that heart disease is the western world’s leading cause of death and illness.
If that picture seems bleak, two teams of scientists have some heartening news for you. The first has found that the heart does actually have the ability to renew its cells, albeit to a limited degree. And the second group has discovered a cocktail of proteins can nudge this process along, at least in mice.
The heart is made of an exclusive breed of cells called cardiomyocytes, whose synchronised contractions provide the heart with its beat. The cardiomyocytes develop from a more basic layer of cells called the mesoderm, which also gives rise to bones, cartilage and other tissues. Now, Jun Takeuchi and Benoit Bruneau from the Gladstone Institute of Cardiovascular Disease have found that a cocktail of three proteins – Gata4, Tbx5 and Baf60c – are enough to transform mesodermal cells into beating cardiomyocytes.
All three are needed for the job. Together, they managed to switch on the full gamut of genes needed to program the mesoderm of embryonic mice into heart cells. When they were added, Takeuchi and Bruneau found signs of various proteins that are associated with developing embryonic hearts, even in parts of the mesoderm that would normally not turn into heart muscle. These out-of-place cells developed very quickly too, for they started beating before the mice’s own heart cells did.
That’s a massive achievement and one that’s completely unprecedented for mammals. Other groups have tried to use protein combos to produce cardiomyocytes in other species, but with little success. In chicks, certain combinations switched on genes involved in heart development, but never went the whole way. In frogs or zebrafish, which have simpler hearts, two proteins were used to produce heart cells, but with just a one in ten success rate. Takeuchi and Bruneau managed to do the same in 9 out of 11 mouse embryos.