Glucocorticoids are active players and therapeutic targets in atherosclerotic cardiovascular disease

Adrenal-derived glucocorticoids mediate the physiological response to stress. Chronic disturbances in glucocorticoid homeostasis, i.e. in Addison's and Cushing's disease patients, predispose to the development of atherosclerotic cardiovascular disease. Here we review preclinical and clinical findings regarding the relation between changes in plasma glucocorticoid levels and the atherosclerosis extent. It appears that, although the altered glucocorticoid function can in most cases be restored in the different patient groups, current therapies do not necessarily reverse the associated risk for atherosclerotic cardiovascular disease. In our opinion much attention should therefore be given to the development of a Cushing's disease mouse model that can (1) effectively replicate the effect of hypercortisolemia on atherosclerosis outcome observed in humans and (2) be used to investigate, in a preclinical setting, the relative impact on atherosclerosis susceptibility of already available (e.g. metyrapone) and potentially novel (i.e. SR-BI activity modulators) therapeutic agents that target the adrenal glucocorticoid output. •Glucocorticoids impact both metabolic and inflammatory processes.•Chronic changes in glucocorticoid status predispose to cardiovascular disease.•Glucocorticoids elicit variable effects on atherosclerosis in preclinical models.•Current Cushing's treatments do no effectively reverse the cardiovascular risk.•Adrenal cholesterol metabolism may serve as novel target in Cushing's syndrome.