Gene switch found to help a heart heal itself

It may one day be possible to fully heal a heart following a heart attack.

Because heart cells lose their ability to divide soon after we are born, when the cells die ? in a heart attack, say ? the dead tissue is replaced by scar tissue rather than new muscle. Now Mauro Giacca of the International Centre for Genetic Engineering and Biotechnology in Trieste, Italy, and his colleagues have identified molecules that stimulate adult heart cells to divide and multiply. The work raises hopes that the cells can be coaxed into doing that later in life, giving damaged hearts a chance to fully recover.

MicroRNAs are short RNA sequences that turn genes on or off. To see which are involved in heart-cell division, Giacca's team tested 875 human microRNAs in cultured rodent heart muscle. They found 204 that reactivated cell proliferation, including two that affected nearly 2000 genes.

Repair trigger

The team induced heart attacks in adult mice and then injected the edge of the damaged area with a harmless virus carrying the two most potent microRNAs. "The idea is to trigger repair of this dead part not through formation of a scar, but through regeneration of the neighbouring tissue," says Giacca.

Two weeks later, the extent of the damage was much less in mice that were injected with the microRNAs, and the strength of contraction and other measures of heart performance were better preserved. What's more, the affected tissue was full of mature muscle cells that were multiplying.

Giacca says this could be a valuable therapeutic intervention after heart attacks in humans, as long as the microRNAs don't cause other kinds of cells to divide, possibly causing cancers.

As using a live virus in humans might also pose a risk, Giacca wants to make synthetic microRNAs packaged in lipids that will deliver the microRNAs intact to damaged hearts.

Journal reference: Nature, DOI:10.1038/nature11739

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