Research ArticlePhysiology

Cardiomyocyte glucocorticoid and mineralocorticoid receptors directly and antagonistically regulate heart disease in mice

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Science Signaling  16 Apr 2019:
Vol. 12, Issue 577, eaau9685
DOI: 10.1126/scisignal.aau9685

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A balancing act for the heart

Stress increases the risk of dying from cardiometabolic disease. In humans, stress triggers the release of the hormone cortisol, which alters gene expression through activation of the glucocorticoid receptor and the structurally related mineralocorticoid receptor. Oakley et al. (see also the Focus by Chapman) generated mice with a cardiomyocyte-specific deficiency in the glucocorticoid receptor, the mineralocorticoid receptor, or both receptors. Mice that were deficient in the mineralocorticoid receptor or both receptors did not develop the heart failure seen in mice deficient in the glucocorticoid receptor. Reexpression of the mineralocorticoid receptor in the double knockout mice resulted in the development of heart failure. These results suggest that mineralocorticoid receptor antagonists are cardioprotective in patients because they promote signaling through glucocorticoid receptors.

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