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- Title
Acute cardiovascular protective effects of corticosteroids are mediated by non-transcriptional activation of endothelial nitric oxide synthase.
- Authors
Hafezi-Moghadam, Ali; Simoncini, Tommaso; Yang, Zequan; Limbourg, Florian P.; Plumier, Jean-Christophe; Rebsamen, Michela C.; Hsieh, Chung-Ming; Chui, Dao-Shan; Thomas, Kennard L.; Prorock, Alyson J.; Laubach, Victor E.; Moskowitz, Michael A.; French, Brent A.; Ley, Klaus; Liao, James K.
- Abstract
Corticosteroids have been shown to exert beneficial effects in the treatment of acute myocardial infarction, but the precise mechanisms underlying their protective effects are unknown. Here we show that high-dose corticosteroids exert cardiovascular protection through a novel mechanism involving the rapid, non-transcriptional activation of endothelial nitric oxide synthase (eNOS). Binding of corticosteroids to the glucocorticoid receptor (GR) stimulated phosphatidylinositol 3-kinase and protein kinase Akt, leading to eNOS activation and nitric oxide?dependent vasorelaxation. Acute administration of pharmacological concentrations of corticosteroids in mice led to decreased vascular inflammation and reduced myocardial infarct size following ischemia and reperfusion injury. These beneficial effects of corticosteroids were abolished by GR antagonists or eNOS inhibitors in wild-type mice and were completely absent in eNOS-deficient (Nos3-/-) mice. The rapid activation of eNOS by the non-nuclear actions of GR, therefore, represents an important cardiovascular protective effect of acute high-dose corticosteroid therapy.
- Subjects
CORTICOSTEROIDS; CARDIOVASCULAR system
- Publication
Nature Medicine, 2002, Vol 8, Issue 5, p473
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/nm0502-473