| Cardiac and Vascular Atrogin-1 mRNA Expression is Not Associated with Dexamethasone Efficacy in the Monocrotaline Model of Pulmonary Hypertension. | |
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MedLine Citation:
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PMID: 22311109 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Atrophic signaling elements of the ubiquitin-proteasome system (UPS) are involved in skeletal muscle wasting as well as pressure overload models of heart failure. In our prior experiments, we demonstrated a transcriptional downregulation of atrophy-inducing vascular E3 ubiquitin ligases in a toxic model of pulmonary hypertension where pulmonary artery and right ventricle (RV) hypertrophy are evident. Given the numerous reports of glucocorticoid activation of the UPS and the negative regulator of muscle mass, myostatin, we investigated the efficacy of dexamethasone to reverse monocrotaline (MCT)-induced pulmonary hypertension and augment atrogin-1 expression in both pulmonary arteries and myocardium. Dexamethasone caused significant reductions in body weight in combination with MCT. As predicted, MCT-induced pulmonary hypertension was evident by increases in RV systolic pressure, right ventricle to left ventricle plus septal weight ratios (RV/LVS) and arterial remodeling. MCT treatment significantly reduced both RV and PA atrogin-1 expression. Dexamethasone treatment reversed the MCT-induced pathological indices and restored RV atrogin-1 expression, but did not impact atrogin-1 expression in pulmonary arteries. Myostatin was poorly expressed in pulmonary arteries compared to the RV, and dexamethasone treatment increase RV myostatin in controls but not MCT-treated rats. These findings suggest that mechanisms independent of myostatin/atrogin-1 are responsible for glucocorticoid efficacy in this model of pulmonary hypertension. |
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Authors:
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Michael L Paffett; Meghan M Channell; Jay S Naik; Selita N Lucas; Matthew J Campen |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-2-7 |
Journal Detail:
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Title: Cardiovascular toxicology Volume: - ISSN: 1559-0259 ISO Abbreviation: - Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-2-7 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101135818 Medline TA: Cardiovasc Toxicol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Pharmaceutical Sciences, MSC09 5360, College of Pharmacy, University of New Mexico, Albuquerque, NM, 87131-0001, USA, mpaffett@salud.unm.edu. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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