Document Detail


Loss of interstitial collagen causes structural and functional alterations of cardiomyocyte subsarcolemmal mitochondria in acute volume overload.
MedLine Citation:
PMID:  21059354     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Volume overload (VO) caused by aortocaval fistula (ACF) is associated with oxidative/inflammatory stress. The resulting inflammation, matrix metalloproteinase (MMP) activation, and collagen degradation is thought to play a pivotal role in left ventricular (LV) dilatation and failure. Since mitochondria are also targets for inflammation and oxidative stress, we hypothesized that there would be bioenergetic dysfunction with acute VO. In Sprague-Dawley rats subjected to 24 hrs of ACF, there was a two-fold increase in LV pressure-volume area in vivo, consistent with increased LV myocardial oxygen usage and increased bioenergetic demand in cardiomyocytes. Isolated cardiomyocytes from ACF LVs demonstrated increased hydrogen peroxide and superoxide formation and increased MMP activity. Subsarcolemmal mitochondria (SSM) showed a 40% decrease in state 3 respiration and proteomic analysis of SSM demonstrated decreased levels of complexes I-V in ACF. Immunohistochemical analysis revealed disruption of the subsarcolemmal location of the SSM network in ACF. To test for a potential link between SSM dysfunction and loss of interstitial collagen, rats were treated with the MMP-inhibitor PD166793 prior to ACF. MMP-inhibitor preserved interstitial collagen, integrin-α5 and the SSM structural arrangement. In addition, the decrease in state 3 mitochondrial respiration with ACF was prevented by PD166793. These studies established an important interaction between degradation of interstitial collagen in acute VO and the disruption of SSM structure and function which could contribute to progression to heart failure.
Authors:
Elena Ulasova; James D Gladden; Yuanwen Chen; Junying Zheng; Betty Pat; Wayne Bradley; Pamela Powell; Jaroslaw W Zmijewski; Blake R Zelickson; Scott W Ballinger; Victor Darley-Usmar; Louis J Dell'italia
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-11-06
Journal Detail:
Title:  Journal of molecular and cellular cardiology     Volume:  50     ISSN:  1095-8584     ISO Abbreviation:  J. Mol. Cell. Cardiol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-10     Completed Date:  2011-05-10     Revised Date:  2014-09-09    
Medline Journal Info:
Nlm Unique ID:  0262322     Medline TA:  J Mol Cell Cardiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  147-56     Citation Subset:  IM    
Copyright Information:
Copyright © 2010. Published by Elsevier Ltd.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blotting, Western
Collagen / metabolism*
Echoencephalography
Immunohistochemistry
Microscopy, Confocal
Microscopy, Electron, Transmission
Mitochondria, Heart / metabolism*,  ultrastructure
Myocytes, Cardiac / metabolism*,  ultrastructure
Oxidative Stress / physiology
Rats
Rats, Sprague-Dawley
Ventricular Function, Left / physiology
Grant Support
ID/Acronym/Agency:
P50 HL077100/HL/NHLBI NIH HHS; P50 HL077100-05/HL/NHLBI NIH HHS; P50HL077100/HL/NHLBI NIH HHS; R01 HL097176/HL/NHLBI NIH HHS; R01 HL097176-01A1/HL/NHLBI NIH HHS; R01 HL097176-03/HL/NHLBI NIH HHS; R01 HL54816/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
9007-34-5/Collagen
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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