Document Detail

SERCA1 expression enhances the metabolic efficiency of improved contractility in post-ischemic heart.
MedLine Citation:
PMID:  19744494     Owner:  NLM     Status:  MEDLINE    
Myocardial stunning is characterized by a metabolic uncoupling from function as mitochondrial tricarboxylic acid (TCA) cycle and oxygen consumption remain normal despite reduced contractility. Overexpression of the sarco-endoplasmic reticulum Ca2+-ATPase (SERCA1) in hearts has recently been reported to reduce dysfunction at reperfusion. In this study we determine whether the metabolic coupling to function improves with SERCA treatment. PBS (control) or adenovirus carrying the cDNA for SERCA1 was delivered via coronary perfusion in vivo to Sprague-Dawley rat hearts. Three days following gene transfer, isolated hearts were perfused with 0.4 mM [2,4,6,8,10,12,14,16-13C8] palmitate and 5 mM glucose, and subjected to 15-min ischemia followed by 40-min reperfusion. Consistent with myocardial stunning, rate pressure product (RPP) and left ventricular developed pressure (LVDP) were depressed 30-40% (p<0.05) in the PBS group. With SERCA1 overexpression, dP/dt was 20% greater than controls (p<0.05), and LVDP and RPP recovered to pre-ischemic values. From dynamic 13C NMR, TCA cycle flux at reperfusion was similar to pre-ischemic values for both groups. Therefore, the efficiency of coupling between cardiac work and TCA cycle flux was restored with SERCA1 treatment. Oxidative efficiency was also enhanced with SERCA1 as cytosolic NADH transport into the mitochondria was significantly greater compared to the PBS group. In addition, the phosphocreatine to ATP ratio (PCr/ATP) was not compromised with SERCA1 expression, despite enhanced function, and depressed fatty acid oxidation at 40-min reperfusion in the PBS group was not reversed with SERCA1. These data demonstrate that metabolic coupling and NADH transport are significantly improved with SERCA1 treatment.
J Michael O'Donnell; Kayla Pound; Xianyao Xu; E Douglas Lewandowski
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural     Date:  2009-09-08
Journal Detail:
Title:  Journal of molecular and cellular cardiology     Volume:  47     ISSN:  1095-8584     ISO Abbreviation:  J. Mol. Cell. Cardiol.     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-10-13     Completed Date:  2009-12-24     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  0262322     Medline TA:  J Mol Cell Cardiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  614-21     Citation Subset:  IM    
Program in Integrative Cardiac Metabolism, Cardiovascular Research Center, Department of Physiology & Biophysics, College of Medicine, University of Illinois at Chicago, 835 South Wolcott Avenue (M/C 901), Chicago, IL 60612, USA.
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MeSH Terms
Adenosine Triphosphate / metabolism
Energy Metabolism / drug effects,  genetics
Heart / drug effects*
Magnetic Resonance Spectroscopy
Mitochondria, Heart / drug effects,  metabolism
Models, Biological
Myocardial Reperfusion Injury / metabolism,  physiopathology
Myocardial Stunning
Myocardium / metabolism*
Oxidation-Reduction / drug effects
Palmitates / metabolism
Phosphocreatine / metabolism
Rats, Sprague-Dawley
Sarcoplasmic Reticulum Calcium-Transporting ATPases / genetics,  pharmacology*,  physiology*
Grant Support
Reg. No./Substance:
0/Palmitates; 56-65-5/Adenosine Triphosphate; 67-07-2/Phosphocreatine; EC Reticulum Calcium-Transporting ATPases

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