How Can You Mend A Broken Heart? Activate the molecular machinery

Researchers at the Salk Institute, La Jolla, Calif, have repaired injured hearts in mice by reviving long-inactive molecular machinery in the animals’ cells, which may lead to new therapies for human heart ailments. The mice exhibited dramatic improvement in heart regeneration and healing after the researchers blocked four molecules believed to suppress these programs for regenerating organs. The scientists theorize that adult mammals mayretain a latent ability to regenerate damaged tissue as a holdover. The researchers note that information needed to generate an organ is contained in the genomes of each cell in the human body. Their findings furnish proof-of-concept for a new type of clinical treatment in the battle against heart disease, which kills about 600,000 people annually in the United States. Juan Carlos Izpisua Belmonte, PhD, professor in the Gene Expression Laboratory at Salk, and his research team chose to concentrate on microRNAs, in some measure because these short strings of RNA control the expression of many genes. They discovered four specific molecules–MiR-99, MiR-100, Let-7a and Let-7c–that met their criteria. These molecules were profoundly repressed during heart injury in zebrafish—and also exist in mice and humans. Studies of cultured mammalian cells and studies of mice with heart damage showed the levels of these molecules were high in adults, and they did not slump with injury. The researchers used adeno-associated viruses peculiar to the heart to target each of those four microRNAs, suppressing their levels experimentally. They found that injecting the inhibitors into the hearts of mice that had suffered a heart attack triggered the regeneration of cardiac cells, boosting the thickness of the heart’s walls and its ability to pump blood—advances that were seen up to six months post-treatment. The team plans to progress to larger animals and see whether this methodology can work in larger hearts, and for longer periods post-treatment. Image: An injured zebrafish heart showing proliferating cells in the wounded area of the heart (red) and cardiac muscle cells (green). [Image: Courtesy of the Salk Institute for Biological Studies]