Document Detail


Acute myocardial rescue with endogenous endothelial progenitor cell therapy.
MedLine Citation:
PMID:  20719564     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Post-myocardial infarction heart failure is a major health concern with limited therapy. Molecular revascularisation utilising granulocyte-macrophage colony stimulating factor (GMCSF) mediated endothelial progenitor cell (EPC) upregulation and stromal cell derived factor-1α (SDF) mediated myocardial EPC chemokinesis, may prevent myocardial loss and adverse remodelling. Vasculogenesis, viability, and haemodynamic improvements following therapy were investigated.
PROCEDURES: Lewis rats (n=91) underwent LAD ligation and received either intramyocardial SDF and subcutaneous GMCSF or saline injections at the time of infarction. Molecular and haemodynamic assessments were performed at pre-determined time points following ligation.
FINDINGS: SDF/GMCSF therapy upregulated EPC density as shown by flow cytometry (0.12±0.02% vs. 0.06±0.01% circulating lymphocytes, p=0.005), 48hours following infarction. A marked increase in perfusion was evident eight weeks after therapy, utilising confocal angiography (5.02±1.7×10(-2)μm(3)blood/μm(3)myocardial tissue vs. 2.03±0.710(-2)μm(3)blood/μm(3)myocardial tissue, p=0.00004). Planimetric analysis demonstrated preservation of wall thickness (0.98±0.09mm vs. 0.67±0.06mm, p=0.003) and ventricular diameter (7.81±0.99mm vs. 9.41±1.1mm, p=0.03). Improved haemodynamic function was evidenced by echocardiography and PV analysis (ejection fraction: 56.4±18.1% vs. 25.3±15.6%, p=0.001; pre-load adjusted maximal power: 6.6±2.6mW/μl(2) vs. 2.7±1.4mW/μl(2), p=0.01).
CONCLUSION: Neovasculogenic therapy with GMCSF-mediated EPC upregulation and SDF-mediated EPC chemokinesis maybe an effective therapy for infarct modulation and preservation of myocardial function following acute myocardial infarction.
Authors:
Pavan Atluri; Corinna M Panlilio; George P Liao; William Hiesinger; David Andrew Harris; Ryan C McCormick; Jeffrey E Cohen; Tao Jin; Wei Feng; Rebecca D Levit; Nianguo Dong; Y Joseph Woo
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-08-16
Journal Detail:
Title:  Heart, lung & circulation     Volume:  19     ISSN:  1444-2892     ISO Abbreviation:  Heart Lung Circ     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-18     Completed Date:  2011-03-18     Revised Date:  2014-09-02    
Medline Journal Info:
Nlm Unique ID:  100963739     Medline TA:  Heart Lung Circ     Country:  Australia    
Other Details:
Languages:  eng     Pagination:  644-54     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Australasian Society of Cardiac and Thoracic Surgeons and the Cardiac Society of Australia and New Zealand. Published by Elsevier B.V. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis
Chemokine CXCL12 / pharmacology,  therapeutic use*
Echocardiography
Endothelial Cells / drug effects*
Flow Cytometry
Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology,  therapeutic use*
Heart / drug effects*
Heart Ventricles / anatomy & histology
Hematopoietic Stem Cells / physiology
Hemodynamics / drug effects*
Male
Models, Animal
Myocardial Infarction / drug therapy*
Myocardium / pathology
Neovascularization, Physiologic / drug effects*
Rats
Rats, Inbred Lew
Up-Regulation
Ventricular Function, Left / drug effects*
Grant Support
ID/Acronym/Agency:
1 F32 HL79769-01/HL/NHLBI NIH HHS; HL072812/HL/NHLBI NIH HHS; K08 HL072812/HL/NHLBI NIH HHS; K08 HL072812-01A1/HL/NHLBI NIH HHS; R01 HL089315/HL/NHLBI NIH HHS; R01 HL089315/HL/NHLBI NIH HHS; R01 HL089315-02/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Chemokine CXCL12; 83869-56-1/Granulocyte-Macrophage Colony-Stimulating Factor
Comments/Corrections

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