In a major step toward restoring damaged cardiovascular tissue, researchers at Sanford Burnham Prebys have discovered that temporarily altering muscle cell metabolism can stimulate multi-cellular regeneration and recover heart function in mice following a heart attack.
While newborn mammals retain the innate capacity to repair cardiac tissue during their first days of life, adult hearts typically replace dead muscle with non-contractile scar tissue rather than new cells. To determine whether this dormant regenerative ability could be reawakened, the research team targeted an enzyme known as succinate dehydrogenase, which plays a central role in mitochondrial fuel processing. By using a compound called malonate, the scientists temporarily inhibited this enzyme, shifting adult heart cells toward a metabolic profile characteristic of the neonatal stage.
This metabolic shift prompted specialized heart muscle cells, known as cardiomyocytes, to divide and multiply across injured areas. Crucially, the intervention extended beyond muscle tissue to orchestrate cooperative repairs among multiple types of cells in the organ. The treatment fostered the growth of new blood vessels while suppressing hyperactive fibroblasts that typically generate rigid scar tissue.
The authors emphasized that dividing cardiomyocytes alone cannot rescue cardiac performance; dampening fibroblast activity proved equally critical for restoring normal pumping capability. Because the metabolic inhibition was transient rather than permanent, the cells were able to complete healing before switching back to the mature metabolic state required for daily cardiac function. Published in *Nature Cardiovascular Research*, the findings point toward new therapeutic avenues that may one day help human heart attack survivors mend their own hearts.