Heart health is dependent on the synergy of two proteins in new mouse study

April 18, 2019

Scientists at the National Institutes of Health and other researchers have discovered two proteins studies in the hearts of mice – stress hormone receptors glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) – work in tandem to keep the muscle healthy.

When these receptors weren’t working together, the mice developed heart disease. The hope is to use the results to create therapies for people at risk of a heart attack. The work was published April 16 in Science Signaling.

We now know from plenty of research that stress can damage the health and well-being of people. It increases the risk a person will develop and even die from heart failure because stress stimulates the body’s adrenal glands to pump more cortisol. This hormone affixes to GRs and MRs in different body tissues during periods of stress in an effort to reduce inflammation and other reactions. Prolonged activation of cortisol, however, raises the level to a degree that is harmful, and can lead to high blood pressure and glucose and unhealthy cholesterol – factors that cause heart disease. 

Much earlier research conducted by this study’s lead author Robert Oakley, Ph.D. and John Cidlowski, Ph.D, revealed that high levels of bad GR increased risk of heart disease. In this study, when the research team tested a mouse strain without heart GR the mice spontaneously developed enlarged hearts, had heart failure, and died while a mouse strain missing cardiac MR allowed the hearts to function normally. The team then tested without either of receptors in the heart tissue, expecting the mice would have the same or worse heart problems as the mice without GR.

"To our surprise the hearts were resistant to heart disease," Oakley said in the NIH release.

Cidlowski suggested 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.

"We propose that since GR and MR cooperate, a better approach is to make a drug that works on both receptors simultaneously," Cidlowski said in the NIH release. "It could help patients with heart disease and prevent subsequent heart diseases."