Stress is linked with heart disease. Perhaps counterintuitively, experiments in mice now reveal the absence of stress may cause them to die prematurely from heart failure, report results detailed this week in the Proceedings of the National Academy of Sciences.
The primary stress hormones in humans are glucocorticoids, which people release from their adrenal glands. They act on numerous target tissues to regulate a wide variety of biological processes, and can have potent anti-inflammatory and immunosuppressive activity.
“Although glucocorticoids are thought of as stress hormones, they’re present in the body all the time, are there every single day — they’re hormones we need for life,” says molecular endocrinologist John Cidlowski at the National Institute of Environmental Health Sciences in Research Triangle Park, N.C.
To learn what role glucocorticoids might play in the heart, Cidlowski with molecular endocrinologist Robert Oakley at the National Institute of Environmental Health Sciences and their colleagues experimentally generated mice that specifically lacked the glucocorticoid receptor in heart muscle cells. The glucocorticoid receptor is what enables cells to respond to glucocorticoids, and overall regulates the activity of about 25 percent of the body’s genes.
The researchers found these mice died prematurely from spontaneous heart failure. By three months of age, these rodents displayed marked problems with heart function, and their hearts were enlarged.
“An enlarged heart is not necessarily a bad thing for the heart — highly trained athletes all have large hearts — but it can often be a predecessor to heart disease,” Cidlowski says.
Before the hearts of these mice became obviously diseased, researchers found they had aberrant activity in a large set of genes linked with heart disease, such as ones helping the heart contract, ones promoting the survival of heart muscle cells and ones repressing enlargement of the heart. Aberrant activity was also seen in genes linked with inflammation.
Although too much stress is linked with heart disease, these findings suggest the presence of stress hormones such as glucocorticoids is also key for maintaining normal heart function.
“There’s a good side to stress — not all stress is bad,” Cidlowski says.
Pharmaceutical companies developing heart medicines are currently targeting another major class of stress hormones, mineralocorticoids. “I think they’d get more bang for their buck if they had a drug that targeted receptors for both glucocorticoids and mineralocorticoids,” Cidlowski says. “Both are clearly important in heart disease.”
Still, the implications of this rodent study are not yet proven in humans, Cidlowski says. “We plan on doing those studies,” he added. “It’s just going to take a little more work.”