Document Detail


Aging impairs the beneficial effect of granulocyte colony-stimulating factor and stem cell factor on post-myocardial infarction remodeling.
MedLine Citation:
PMID:  16873716     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF) are potential new therapies to ameliorate post-myocardial infarction (post-MI) remodeling, as they enhance endogenous cardiac repair mechanisms and decrease cardiomyocyte apoptosis. Because both of these pathways undergo alterations with increasing age, we hypothesized that therapeutic efficacy of G-CSF and SCF is impaired in old versus young adult rats. MI was induced in 6- and 20-month-old rats by permanent ligation of the left coronary artery. In young animals, G-CSF/SCF therapy stabilized and reversed a decline in cardiac function, attenuated left ventricular dilation, decreased infarct size, and reduced cardiomyocyte hypertrophy. Remarkably, these effects on cardiac structure and function were absent in aged rodents. This could not be attributed to ineffective mobilization of bone marrow cells or decreased quantity of c-Kit(+) cells within the myocardium with aging. However, whereas the G-CSF/SCF cocktail reduced cardiac myocyte apoptosis in old as well as in young hearts, the degree of reduction was substantially less with age and the rate of cardiomyocyte apoptosis in old animals remained high despite cytokine treatment. These findings demonstrate that G-CSF/SCF lacks therapeutic efficacy in old animals by failing to offset periinfarct apoptosis and therefore raise important concerns regarding the efficacy of novel cytokine therapies in elderly individuals at greatest risk for adverse consequences of MI.
Authors:
Stephanie Lehrke; Ramesh Mazhari; Daniel J Durand; Meizi Zheng; Djahida Bedja; Jeffrey M Zimmet; Karl H Schuleri; Andrew S Chi; Kathleen L Gabrielson; Joshua M Hare
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-07-27
Journal Detail:
Title:  Circulation research     Volume:  99     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-09-01     Completed Date:  2006-10-02     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  553-60     Citation Subset:  IM    
Affiliation:
Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
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MeSH Terms
Descriptor/Qualifier:
Adaptation, Physiological
Aging*
Animals
Antigens, CD34 / metabolism
Apoptosis / drug effects
Blood Cell Count
Blood Cells / metabolism
Blotting, Western
Drug Combinations
Echocardiography
Granulocyte Colony-Stimulating Factor / pharmacology*
Heart / physiopathology
Hypertrophy
Myocardial Infarction / metabolism,  physiopathology*,  ultrasonography
Myocytes, Cardiac / metabolism,  pathology
Proto-Oncogene Proteins c-kit / metabolism
Rats
Rats, Inbred F344
Stem Cell Factor / pharmacology*
Ventricular Remodeling / drug effects*
Grant Support
ID/Acronym/Agency:
R01 HL-65455/HL/NHLBI NIH HHS; R01 NIA AG078915/AG/NIA NIH HHS; R21 HL-72185/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD34; 0/Drug Combinations; 0/Stem Cell Factor; 143011-72-7/Granulocyte Colony-Stimulating Factor; EC 2.7.10.1/Proto-Oncogene Proteins c-kit

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


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