Abstract
Corticosteroids influence the development and function of the heart and its response to injury and pressure overload via actions on glucocorticoid (GR) and mineralocorticoid (MR) receptors. Systemic corticosteroid concentration depends largely on the activity of the hypothalamic–pituitary–adrenal (HPA) axis, but glucocorticoid can also be regenerated from intrinsically inert metabolites by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), selectively increasing glucocorticoid levels within cells and tissues. Extensive studies have revealed the roles for glucocorticoid regeneration by 11β-HSD1 in liver, adipose, brain and other tissues, but until recently, there has been little focus on the heart. This article reviews the evidence for glucocorticoid metabolism by 11β-HSD1 in the heart and for a role of 11β-HSD1 activity in determining the myocardial growth and physiological function. We also consider the potential of 11β-HSD1 as a therapeutic target to enhance repair after myocardial infarction and to prevent the development of cardiac remodelling and heart failure.
Highlights
The major physiological adrenocorticosteroid hor mones, glucocorticoids and mineralocorticoids are vital for normal cardiovascular function
We have found that targeted deletion of 11β-HSD1 in cardiomyocytes and vascular smooth muscle cells leads to a significant reduction in Hsd11b1 gene expression in the mouse heart, confirming its expression in these cells (White et al 2016)
Recent studies have shown that 11β-HSD1 is expressed in myocardial cells, including notably cardiac fibroblasts
Summary
The major physiological adrenocorticosteroid hor mones, glucocorticoids (cortisol in most animals and corticosterone in rats and mice) and mineralocorticoids (aldosterone) are vital for normal cardiovascular function. They regulate blood pressure (Hunter & Bailey 2015) and vascular tone (Ullian 1999, Dover et al 2007, Hadoke et al 2009), as well as heart rhythm and contractility (Lefer 1967, 1968, Penefsky & Kahn 1971, Ouvrard-Pascaud et al 2005, Cruz-Topete et al 2016). Rapid corticosteroid release in response to hypothalamic– pituitary–adrenal (HPA) axis activation is an early response to cardiovascular insult, including after myocardial infarction (MI).
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