Little is understood about how physical activity influences the heart itself even though its benefits are well-known.
Now, a new study offers some of the first molecular-level insights.
The studies in mice has suggested that exercise turns on a genetic program that leads the heart to grow as heart muscle cells divide.
It appears that shift in activity is driven in part by a single transcription factor (a gene that controls other genes). That gene, known as C/EBPb, was known to play important roles in other parts of the body, but this is the first evidence for its influence in the heart.
"We've identified a pathway involved in beneficial cardiac hypertrophy - the good kind of heart growth," said Bruce Spiegelman of Harvard Medical School.
The findings may have clinical implications, particularly for those with heart failure or other conditions that make exercise difficult to impossible, said the researchers.
Anthony Rosenzweig, of Harvard Medical School, said, "In the longer term, by understanding the pathways that benefit the heart with exercise, we may be able to exploit those for patients who aren't able to exercise. If there were a way to modulate the same pathway in a beneficial way, it would open up new avenues for treatment."
The researchers found changes in 175 transcription factors in exercised mice and 96 in mice whose aortas were constricted. Importantly, the changes showed little overlap between the two animal models.
For instance, the researchers said, 13 percent of the genes with differential expression following exercise have known or suggested roles in cell proliferation compared to less than one percent of those that changed with the surgery.
Studies in animals and cell culture also showed that the decline in C/EPBb leads to changes that appear to be consistent with those that follow endurance exercise, including an increase in heart muscle size and proliferation. Those mice with lower C/EPBb levels also were resistant to heart failure.
That finding is key given that there is little prior evidence showing that the increase in heart size with exercise has direct benefits, said the researchers.
The study was published in the journal Cell, a Cell Press publication.