Getting to the heart of intracellular glucocorticoid regeneration: 11β-HSD1 in the myocardium.
Getting to the heart of intracellular glucocorticoid regeneration: 11β-HSD1 in the myocardium.
复制标题
到达细胞内糖皮质激素再生的心脏：心肌中的11β-HSD1。
DOI：
10.1530/jme-16-0128
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发表时间：
2017-01
影响因子：
3.5
通讯作者：
Chapman KE
中科院分区：
文献类型：
--
作者：
Gray GA;White CI;Castellan RF;McSweeney SJ;Chapman KE
皮质类固醇通过作用于糖皮质激素（GR）和盐皮质激素（MR）受体，影响心脏的发育和功能，以及心脏对损伤和压力超负荷的反应。全身皮质类固醇浓度在很大程度上取决于下丘脑-垂体-肾上腺（HPA）轴的活性，但糖皮质激素也可以通过11β-羟基类固醇脱氢酶1（11β-HSD 1）从固有惰性代谢产物中再生，选择性增加细胞和组织内的糖皮质激素水平。广泛的研究已经揭示了11β-HSD 1在肝脏、脂肪、大脑和其他组织中对糖皮质激素再生的作用，但直到最近，对心脏的关注还很少。本文综述了11β-HSD 1在心脏糖皮质激素代谢中的作用以及11β-HSD 1活性在心肌生长和生理功能中的作用。我们还考虑了11β-HSD 1作为治疗靶点的潜力，以增强心肌梗死后的修复，并防止心脏重塑和心力衰竭的发展。
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.