TY - JOUR
T1 - Acute Myocardial Rescue with Endogenous Endothelial Progenitor Cell Therapy
AU - Atluri, Pavan
AU - Panlilio, Corinna M.
AU - Liao, George P.
AU - Hiesinger, William
AU - Harris, David Andrew
AU - McCormick, Ryan C.
AU - Cohen, Jeffrey E.
AU - Jin, Tao
AU - Feng, Wei
AU - Levit, Rebecca D.
AU - Dong, Nianguo
AU - Woo, Y. Joseph
N1 - Funding Information:
This work was supported in part by grants from the National Institutes of Health (NIH) , National Heart Lung and Blood Institute RO1 HL089315 (Y. Joseph Woo, MD), NIH National Heart Lung and Blood Institute/Thoracic Surgery Foundation for Research and Education HL072812 (Y. Joseph Woo, MD), American Heart Association 0665441U (Y. Joseph Woo, MD), and National Institutes of Health, National Heart Lung Blood Institute – Ruth L. Kirschstein National Research Service Award, Individual Fellowship 1 F32 HL79769-01 (Pavan Atluri, MD).
PY - 2010/11
Y1 - 2010/11
N2 - 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±1.7×10-2μm3blood/μm3myocardial tissue vs. 2.03±0.710-2μm3blood/μm3myocardial 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/μl2 vs. 2.7±1.4mW/μl2, 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.
AB - 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±1.7×10-2μm3blood/μm3myocardial tissue vs. 2.03±0.710-2μm3blood/μm3myocardial 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/μl2 vs. 2.7±1.4mW/μl2, 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.
KW - Endothelial progenitor cell
KW - Granulocyte-macrophage colony stimulating factor
KW - Ischaemia
KW - Stromal cell derived factor
KW - Vasculogenesis
UR - http://www.scopus.com/inward/record.url?scp=77957861502&partnerID=8YFLogxK
U2 - 10.1016/j.hlc.2010.06.1056
DO - 10.1016/j.hlc.2010.06.1056
M3 - Article
C2 - 20719564
AN - SCOPUS:77957861502
SN - 1443-9506
VL - 19
SP - 644
EP - 654
JO - Heart Lung and Circulation
JF - Heart Lung and Circulation
IS - 11
ER -