ACTIVATION OF THE MINERALOCORTICOID RECEPTOR BY ENDOGENOUS GLUCOCORTICOIDS IN THE DEVELOPMENT OF CARDIAC FIBROSIS

摘要

Background: The renin-angiotensin-aldosterone system plays amajor role in the pathophysiology of heart failure. Activation of the mineralocorticoid receptor (MR) in the context of a high salt intake produces vascular inflammation and cardiac fibrosis. We have shown that activation of the MR, by endogenous glucocorticoids, when the specificity conferring enzyme 11 betaHSD2 is inactivated, is sufficient to produce a similar pathology. We hypothesise that 11 (3HSD2 activity, as opposed to the occupancy by endogenous glucocorticoids is key to determining the activation state of the MR in normal physiology and pathology.