| Myeloid mineralocorticoid receptor controls macrophage polarization and cardiovascular hypertrophy and remodeling in mice. | |
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MedLine Citation:
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PMID: 20697155 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Inappropriate excess of the steroid hormone aldosterone, which is a mineralocorticoid receptor (MR) agonist, is associated with increased inflammation and risk of cardiovascular disease. MR antagonists are cardioprotective and antiinflammatory in vivo, and evidence suggests that they mediate these effects in part by aldosterone-independent mechanisms. Here we have shown that MR on myeloid cells is necessary for efficient classical macrophage activation by proinflammatory cytokines. Macrophages from mice lacking MR in myeloid cells (referred to herein as MyMRKO mice) exhibited a transcription profile of alternative activation. In vitro, MR deficiency synergized with inducers of alternatively activated macrophages (for example, IL-4 and agonists of PPARgamma and the glucocorticoid receptor) to enhance alternative activation. In vivo, MR deficiency in macrophages mimicked the effects of MR antagonists and protected against cardiac hypertrophy, fibrosis, and vascular damage caused by L-NAME/Ang II. Increased blood pressure and heart rates and decreased circadian variation were observed during treatment of MyMRKO mice with L-NAME/Ang II. We conclude that myeloid MR is an important control point in macrophage polarization and that the function of MR on myeloid cells likely represents a conserved ancestral MR function that is integrated in a transcriptional network with PPARgamma and glucocorticoid receptor. Furthermore, myeloid MR is critical for blood pressure control and for hypertrophic and fibrotic responses in the mouse heart and aorta. |
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Authors:
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Michael G Usher; Sheng Zhong Duan; Christine Y Ivaschenko; Ryan A Frieler; Stefan Berger; Günther Schütz; Carey N Lumeng; Richard M Mortensen |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-08-09 |
Journal Detail:
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Title: The Journal of clinical investigation Volume: 120 ISSN: 1558-8238 ISO Abbreviation: J. Clin. Invest. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-09-02 Completed Date: 2010-12-15 Revised Date: 2012-02-07 |
Medline Journal Info:
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Nlm Unique ID: 7802877 Medline TA: J Clin Invest Country: United States |
Other Details:
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Languages: eng Pagination: 3350-64 Citation Subset: AIM; IM |
Affiliation:
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Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan 48109-5622, USA. |
| Data Bank Information | |
Bank Name/Acc. No.:
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GEO/GSE23308 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aldosterone
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blood,
pharmacology Animals Blood Pressure / drug effects, physiology Cardiomegaly / pathology Cardiovascular Diseases / pathology Fibrosis / pathology Heart / drug effects, physiopathology Hypertension / pathology, physiopathology Hypertrophy / pathology Interleukin-4 / pharmacology Macrophages / drug effects Mice Mice, Knockout Mice, Transgenic NG-Nitroarginine Methyl Ester / pharmacology Receptors, Glucocorticoid / antagonists & inhibitors, physiology Receptors, Mineralocorticoid / antagonists & inhibitors*, genetics, physiology* |
| Grant Support | |
ID/Acronym/Agency:
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K08 DK078851-05/DK/NIDDK NIH HHS; R01HL083201/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/NR3C1 protein, human; 0/Receptors, Glucocorticoid; 0/Receptors, Mineralocorticoid; 207137-56-2/Interleukin-4; 50903-99-6/NG-Nitroarginine Methyl Ester; 52-39-1/Aldosterone |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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