title: Acute myocardial rescue with endogenous endothelial progenitor cell therapy.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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: Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, United States.
authors: Pavan
authors: P
authors: Atluri
authors: Corinna M
authors: CM
authors: Panlilio
authors: George P
authors: GP
authors: Liao
authors: William
authors: W
authors: Hiesinger
authors: David Andrew
authors: DA
authors: Harris
authors: Ryan C
authors: RC
authors: McCormick
authors: Jeffrey E
authors: JE
authors: Cohen
authors: Tao
authors: T
authors: Jin
authors: Wei
authors: W
authors: Feng
authors: Rebecca D
authors: RD
authors: Levit
authors: Nianguo
authors: N
authors: Dong
authors: Y Joseph
authors: YJ
authors: Woo
mesh_terms: D000818:Animals; D017209:Apoptosis; D054377:Chemokine CXCL12 / Q000494:pharmacology / Q000627:therapeutic use*; D004452:Echocardiography; D042783:Endothelial Cells / Q000187:drug effects*; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000033:anatomy & histology; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D023421:Models, Animal; D009203:Myocardial Infarction / Q000188:drug therapy*; D009206:Myocardium / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D011917:Rats, Inbred Lew; D015854:Up-Regulation; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D054377:Chemokine CXCL12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor