| Dynamic molecular and histopathological changes in the extracellular matrix and inflammation in the transition to heart failure in isolated volume overload. | |
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MedLine Citation:
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PMID: 21421827 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Left ventricular (LV) volume overload (VO) causes eccentric remodeling with inflammatory cell infiltration and extracellular matrix (ECM) degradation, for which there is currently no proven therapy. To uncover new pathways that connect inflammation and ECM homeostasis with cellular dysfunction, we determined the cardiac transciptome in subacute, compensated, and decompensated stages based on in vivo hemodynamics and echocardiography in the rat with aortocaval fistula (ACF). LV dilatation at 5 wk was associated with a normal LV end-diastolic dimension-to-posterior wall thickness ratio (LVEDD/PWT; compensated), whereas the early 2-wk (subacute) and late 15-wk (decompensated) ACF groups had significant increases in LVEDD/PWT. Subacute and decompensated stages had a significant upregulation of genes related to inflammation, the ECM, the cell cycle, and apoptosis. These changes were accompanied by neutrophil and macrophage infiltration, nonmyocyte apoptosis, and interstitial collagen loss. At 15 wk, there was a 40-fold increase in the matricellular protein periostin, which inhibits connections between collagen and cells, thereby potentially mediating a side-to-side slippage of cardiomyocytes and LV dilatation. The majority of downregulated genes was composed of mitochondrial enzymes whose suppression progressed from 5 to 15 wk concomitant with LV dilatation and systolic heart failure. The profound decrease in gene expression related to fatty acid, amino acid, and glucose metabolism was associated with the downregulation of peroxisome proliferator associated receptor (PPAR)-α-related and bioenergetic-related genes at 15 wk. In VO, an early phase of inflammation subsides at 5 wk but reappears at 15 wk with marked periostin production along with the suppression of genes related to PPAR-α and energy metabolism. |
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Authors:
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Yuan-Wen Chen; Betty Pat; James D Gladden; Junying Zheng; Pamela Powell; Chih-Chang Wei; Xiangqin Cui; Ahsan Husain; Louis J Dell'italia |
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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: 2011-03-18 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 300 ISSN: 1522-1539 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-06-02 Completed Date: 2011-08-23 Revised Date: 2012-01-31 |
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: H2251-60 Citation Subset: IM |
Affiliation:
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Center for Heart Failure Research, Division of Cardiology, Univ. of Alabama at Birmingham, 434 BMR2, 1530 3rd Ave. S., Birmingham, AL 35294-2180, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Adhesion Molecules / metabolism Disease Progression* Energy Metabolism / physiology Extracellular Matrix / pathology* Heart Failure / metabolism, pathology*, physiopathology Hemodynamics / physiology Inflammation / pathology* Male Models, Animal PPAR alpha / metabolism Rats Rats, Sprague-Dawley Ventricular Dysfunction, Left / metabolism, pathology*, physiopathology Ventricular Remodeling / physiology |
| Grant Support | |
ID/Acronym/Agency:
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P50 HL077100-05/HL/NHLBI NIH HHS; P50-HL-077100/HL/NHLBI NIH HHS; R01 HL097176-01A1/HL/NHLBI NIH HHS; R01 HL097176-03/HL/NHLBI NIH HHS; R01-HL-54816/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cell Adhesion Molecules; 0/PPAR alpha; 0/Postn protein, rat |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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