| Muscle ring finger 1 mediates cardiac atrophy in vivo. | |
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MedLine Citation:
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PMID: 19168726 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Pathological cardiac hypertrophy, induced by various etiologies such as high blood pressure and aortic stenosis, develops in response to increased afterload and represents a common intermediary in the development of heart failure. Understandably then, the reversal of pathological cardiac hypertrophy is associated with a significant reduction in cardiovascular event risk and represents an important, yet underdeveloped, target of therapeutic research. Recently, we determined that muscle ring finger-1 (MuRF1), a muscle-specific protein, inhibits the development of experimentally induced pathological; cardiac hypertrophy. We now demonstrate that therapeutic cardiac atrophy induced in patients after left ventricular assist device placement is associated with an increase in cardiac MuRF1 expression. This prompted us to investigate the role of MuRF1 in two independent mouse models of cardiac atrophy: 1) cardiac hypertrophy regression after reversal of transaortic constriction (TAC) reversal and 2) dexamethasone-induced atrophy. Using echocardiographic, histological, and gene expression analyses, we found that upon TAC release, cardiac mass and cardiomyocyte cross-sectional areas in MuRF1(-/-) mice decreased approximately 70% less than in wild type mice in the 4 wk after release. This was in striking contrast to wild-type mice, who returned to baseline cardiac mass and cardiomyocyte size within 4 days of TAC release. Despite these differences in atrophic remodeling, the transcriptional activation of cardiac hypertrophy measured by beta-myosin heavy chain, smooth muscle actin, and brain natriuretic peptide was attenuated similarly in both MuRF1(-/-) and wild-type hearts after TAC release. In the second model, MuRF1(-/-) mice also displayed resistance to dexamethasone-induced cardiac atrophy, as determined by echocardiographic analysis. This study demonstrates, for the first time, that MuRF1 is essential for cardiac atrophy in vivo, both in the setting of therapeutic regression of cardiac hypertrophy and dexamethasone-induced atrophy. |
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Authors:
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Monte S Willis; Mauricio Rojas; Luge Li; Craig H Selzman; Ru-Hang Tang; William E Stansfield; Jessica E Rodriguez; David J Glass; Cam Patterson |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-01-23 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 296 ISSN: 0363-6135 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2009 Apr |
Date Detail:
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Created Date: 2009-03-31 Completed Date: 2009-06-10 Revised Date: 2010-09-23 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H997-H1006 Citation Subset: IM |
Affiliation:
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Carolina Cardiovascular Biology Center, University of North Carolina, Chapel Hill, North Carolina, USA. monte_willis@med.unc.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Actins
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metabolism Animals Atrophy / chemically induced, metabolism, pathology Dexamethasone / adverse effects Disease Models, Animal Heart Diseases / chemically induced, metabolism*, pathology* Heart-Assist Devices Mice Mice, Knockout Muscle Proteins / metabolism* Myocardium / metabolism*, pathology* Myocytes, Cardiac / pathology Natriuretic Peptide, Brain / metabolism Ubiquitin-Protein Ligases / metabolism* Vasoconstriction Ventricular Myosins / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Actins; 0/Muscle Proteins; 114471-18-0/Natriuretic Peptide, Brain; 50-02-2/Dexamethasone; EC 3.6.1.-/Ventricular Myosins; EC 6.3.2.19/Trim63 protein, mouse; EC 6.3.2.19/Ubiquitin-Protein Ligases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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