Document Detail


Mesenchymal stem cell transplantation for the infarcted heart: a role in minimizing abnormalities in cardiac-specific energy metabolism.
MedLine Citation:
PMID:  21971524     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Intense interest has been focused on cell-based therapy for the infarcted heart given that stem cells have exhibited the ability to reduce infarct size and mitigate cardiac dysfunction. Despite this, it is unknown whether mesenchymal stem cell (MSC) therapy can prevent metabolic remodeling following a myocardial infarction (MI). This study examines the ability of MSCs to rescue the infarcted heart from perturbed substrate uptake in vivo. C57BL/6 mice underwent chronic ligation of the left anterior descending coronary artery to induce a MI. Echocardiography was performed on conscious mice at baseline as well as 7 and 23 days post-MI. Twenty-eight days following the ligation procedure, hyperinsulinemic euglycemic clamps assessed in vivo insulin sensitivity. Isotopic tracer administration evaluated whole body, peripheral tissue, and cardiac-specific glucose and fatty acid utilization. To gain insight into the mechanisms by which MSCs modulate metabolism, mitochondrial function was assessed by high-resolution respirometry using permeabilized cardiac fibers. Data show that MSC transplantation preserves insulin-stimulated fatty acid uptake in the peri-infarct region (4.25 ± 0.64 vs. 2.57 ± 0.34 vs. 3.89 ± 0.54 μmol·100 g(-1)·min(-1), SHAM vs. MI + PBS vs. MI + MSC; P < 0.05) and prevents increases in glucose uptake in the remote left ventricle (3.11 ± 0.43 vs. 3.81 ± 0.79 vs. 6.36 ± 1.08 μmol·100 g(-1)·min(-1), SHAM vs. MI + PBS vs. MI + MSC; P < 0.05). This was associated with an enhanced efficiency of mitochondrial oxidative phosphorylation with a respiratory control ratio of 3.36 ± 0.18 in MSC-treated cardiac fibers vs. 2.57 ± 0.14 in the infarct-only fibers (P < 0.05). In conclusion, MSC therapy exhibits the potential to rescue the heart from metabolic aberrations following a MI. Restoration of metabolic flexibility is important given the metabolic demands of the heart and the role of energetics in the progression to heart failure.
Authors:
Curtis C Hughey; Virginia L Johnsen; Lianli Ma; Freyja D James; Pampee P Young; David H Wasserman; Jeffrey N Rottman; Dustin S Hittel; Jane Shearer
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-10-04
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  302     ISSN:  1522-1555     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-01-04     Completed Date:  2012-02-16     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E163-72     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Calgary, 2500 University Dr. NW, Calgary, Alberta, Canada. cchughey@ucalgary.ca
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MeSH Terms
Descriptor/Qualifier:
Animals
Energy Metabolism / physiology*
Heart / physiopathology
Mesenchymal Stem Cell Transplantation*
Mice
Mitochondria / metabolism*,  pathology
Myocardial Infarction / metabolism,  pathology,  physiopathology,  therapy*
Myocardium / metabolism*,  pathology
Phosphorylation / physiology
Ventricular Remodeling / physiology*
Grant Support
ID/Acronym/Agency:
DK-054902/DK/NIDDK NIH HHS; R01 DK054902/DK/NIDDK NIH HHS; R01-HL-088424/HL/NHLBI NIH HHS; U24-DK-059637/DK/NIDDK NIH HHS; //Canadian Institutes of Health Research
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