A healthy heart needs two proteins to work together

A study published in Science Signaling showed that two proteins work in combination with stress hormones to maintain heart health in mice. The study, led by scientists at the National Institutes of Health and their collaborators, may guide the development of therapeutic new drugs to help people with increased risk of a heart attack.

These two proteins are the GR (glucocorticoid receptor) and the MR (mineralocorticoid receptor), which work synergistically to help support heart health. When the signal transmission between the two receptors is out of balance, the mice have heart disease.

When a person is under stress, the adrenal glands in the body secrete a hormone called cortisol. Cortisol is also called stress hormone or stress hormone. When cortisol is elevated, the patient may have abnormal blood pressure, so a person feels pressure for a long time and his risk of dying from heart failure increases. Cortisol participates in fight-or-flight response and combines with GRs and MRs in different tissues of the body to reduce inflammation and other functions. If cortisol is kept too high for a long time, common risk factors may occur such as elevated levels of cholesterol and glucose in the blood or high blood pressure.

Dr. Robert Oakley, the chief author of the study, first discovered a faulty GR in the 1990s. After this discovery, other scientists concluded that people with a higher than normal GR content had a greater risk of heart disease. Based on this finding, the team tested a mouse strain without heart GR in a laboratory at the National Institute of Environmental Health Sciences (NIEHS). The heart of these animals spontaneously expands, leading to heart failure and death. However, when the team designed a mouse that lacked cardiac MR, the heart function of these animals was normal.

These results led the team to wonder what would happen if there is a lack of two receptors in heart tissue, they then produced a mouse strain that lacks both GR and MR.

Contrary to their expected results, mice that knocked out GR and MR at the same time did not have the same or worse heart problems but were resistant to heart disease.

Researchers speculate that this unexpected result may be due to the fact that double knockout mice do not have genetic changes in heart failure like mice lacking GR, but also show enhanced gene function to protect the heart. Although the heart function of these mice was normal, they were slightly enlarged compared to the hearts of mice without MR.

In the past, scientists have developed molecular drugs that can only act on one receptor in the treatment of heart disease. Now that we know that GR and MR work together to maintain heart health, the better way to help and prevent heart disease is to create a drug that works on both receptors.