Healthy hearts need two proteins working together

Two proteins that bind to stress hormones work together to maintain a healthy heart in mice.

These proteins, stress hormone receptors known as the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), act in concert to help support heart health. When the signaling between the two receptors is out of balance, the mice have heart disease.

Stress increases risk of dying from heart failure by inducing adrenal glands to make a hormone called cortisol. Cortisol is involved in the fight-or-flight response and binds to GRs and MRs in different tissues of the body to reduce inflammation, among other functions.

If the level of cortisol remains too high over a long period of time, common risk factors for heart disease may arise, such as increased cholesterol and glucose in the blood and high blood pressure.

Scientists determined that people with above average amounts of this altered GR had greater risk of heart disease.

Based on this finding, scientists tested a mouse strain without heart GR in their lab at the National Institute of Environmental Health Sciences (NIEHS), part of NIH. These animals spontaneously developed enlarged hearts leading to heart failure and death. When the team produced a mouse strain missing cardiac MR, the animals’ hearts functioned normally.

They made another mouse strain that lacked GR and MR. They guessed that these double-knockout mice would have the same or worse heart problems as the mice without GR. But the hearts were resistant to heart disease.

These mice did not have the gene changes that lead to heart failure as seen in mice lacking GR, while simultaneously exhibiting a gain in function of genes that protect the heart. Although the hearts of these mice function normally, they are slightly enlarged compared to the hearts with no MR.

Since GR and MR cooperate, a better approach is to make a drug that works on both receptors simultaneously. It could help patients with heart disease and prevent subsequent heart diseases. (National Institutes of Health)

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