Healthy hearts need two proteins working together

Tuesday, April 16, 2019

NIH research could be a step toward a treatment to prevent heart attacks

Two proteins that bind to stress hormones work together to maintain a healthy heart in mice, according to scientists at the National Institutes of Health and their collaborators. 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.

The work, published April 16 in Science Signaling, may lead to the development of therapeutic compounds that help people with an increased risk of a heart attack.

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.

Lead author Robert Oakley, Ph.D., first identified a malfunctioning GR in the 1990s when he was a graduate student working with John Cidlowski, Ph.D., at the University of North Carolina at Chapel Hill. Soon after the discovery, other scientists determined that people with above average amounts of this altered GR had greater risk of heart disease. Based on this finding, Oakley and Cidlowski 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.