Therapeutic manipulation of glucocorticoid metabolism in cardiovascular disease
Author(s) -
Hadoke Patrick W.F.,
Iqbal Javaid,
Walker Brian R.
Publication year - 2009
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2008.00047.x
Subject(s) - glucocorticoid , glucocorticoid receptor , mineralocorticoid receptor , endocrinology , mineralocorticoid , medicine , biology , receptor , aldosterone
The therapeutic potential for manipulation of glucocorticoid metabolism in cardiovascular disease was revolutionized by the recognition that access of glucocorticoids to their receptors is regulated in a tissue‐specific manner by the isozymes of 11β‐hydroxysteroid dehydrogenase. Selective inhibitors of 11β‐hydroxysteroid dehydrogenase type 1 have been shown recently to ameliorate cardiovascular risk factors and inhibit the development of atherosclerosis. This article addresses the possibility that inhibition of 11β‐hydroxsteroid dehydrogenase type 1 activity in cells of the cardiovascular system contributes to this beneficial action. The link between glucocorticoids and cardiovascular disease is complex as glucocorticoid excess is linked with increased cardiovascular events but glucocorticoid administration can reduce atherogenesis and restenosis in animal models. There is considerable evidence that glucocorticoids can interact directly with cells of the cardiovascular system to alter their function and structure and the inflammatory response to injury. These actions may be regulated by glucocorticoid and/or mineralocorticoid receptors but are also dependent on the 11β‐hydroxysteroid dehydrogenases which may be expressed in cardiac, vascular (endothelial, smooth muscle) and inflammatory (macrophages, neutrophils) cells. The activity of 11β‐hydroxysteroid dehydrogenases in these cells is dependent upon differentiation state, the action of pro‐inflammaotory cytokines and the influence of endogenous inhibitors (oxysterols, bile acids). Further investigations are required to clarify the link between glucocorticoid excess and cardiovascular events and to determine the mechanism through which glucocorticoid treatment inhibits atherosclerosis/restenosis. This will provide greater insights into the potential benefit of selective 11β‐hydroxysteroid dehydrogenase inhibitors in treatment of cardiovascular disease.
Discover
Journals
Proceedings
Books
Explore
Engineering & Computer Science
Health & Medical Sciences
Humanities, Literature & Arts
Life Sciences & Earth Sciences
Physics & Mathematics
Social Sciences
Chemical & Material Sciences
Business, Economics & Management