Glucocorticoid signaling in cardiac disease

Abstract

As major mediators of stress regulation, glucocorticoids have an essential role in maintaining cardiovascular homeostasis under both physiological and pathological conditions. The release of glucocorticoids into the peripheral circulation is adjusted by the hypothalamic-pituitary-adrenal axis in response to various pathological challenges such as sepsis, starvation, and psychological stress. Clinically, dysregulation of the glucocorticoid-mediated signaling as a result of either excess ligand or receptor hypersensitivity is connected with the progression of unfavorable cardiovascular events such as cardiac hypertrophy, atherosclerosis, and coronary artery disease. The direct effects of glucocorticoids on cardiac tissues are mediated by two steroid receptors, the glucocorticoid receptor and mineralocorticoid receptor, which are both expressed by cardiomyocytes. Although each receptor has some shared responses to glucocorticoids, each receptor also has unique effects on cardiac functions. Elucidating the selective actions of each receptor is critical for determining the proper pharmaceutical targets in cardiovascular diseases.

Cardiac Hypertrophy and Related Dysfunctions in Cushing Syndrome Patients—Literature Review

“…Narayanan et al assessed the potential therapeutic benefits of dexamethasone treatment on myocardial function in senescent rats and demonstrated that it can reverse contractile performance by approximately two-fold caused by increased uptake of ATP-energized Ca2+ in the sarcoplasmic reticulum [ 45 ]. In addition, GC potentially inhibits cardiomyocyte apoptosis [ 46 , 47 ] by activating serum and glucocorticoid-responsive kinase (SGK-1), B-cell lymphoma-extra large (Bcl-xL), and growth arrest specific 2 (Gas2) [ 48 , 49 ]. Additionally, GR potentially protects cardiomyocytes from DNA damage and drug-induced cell death by regulating the expression of Kruppel-like factor 13 (KLF13), a major mediator of GR [ 50 ].…”