TY - JOUR
T1 - Induction of angiogenesis and inhibition of apoptosis by hepatocyte growth factor effectively treats postischemic heart failure
AU - Jayasankar, Vasant
AU - Woo, Y. Joseph
AU - Pirolli, Timothy J.
AU - Bish, Lawrence T.
AU - Berry, Mark F.
AU - Burdick, Jeffrey
AU - Gardner, Timothy J.
AU - Sweeney, H. Lee
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/1
Y1 - 2005/1
N2 - Background: Heart failure following myocardial infarction (MI) is a significant cause of morbidity and mortality and remains a difficult therapeutic challenge. Hepatocyte growth factor (HGF) is a potent angiogenic and anti-apoptotic protein whose receptor is upregulated following MI. This study was designed to investigate the ability of HGF to prevent heart failure in a rat model of experimental MI. Methods: The rats underwent direct intramyocardial injection with replication-deficient adenovirus encoding HGF (n = 7) or null virus as control (n = 7) 3 weeks following ligation of the left anterior descending coronary artery. Analysis of the following was performed 3 weeks after injection: cardiac function by pressure-volume conductance catheter measurements; LV wall thickness; angiogenesis by Von Willebrand's factor staining; and apoptosis by the TUNEL assay. The expression levels of HGF and the anti-apoptotic factor Bcl-2 were analyzed by Western blot. Results: Adeno-HGF-treated animals had greater preservation of maximum LV pressure (HGF 77 ± 3 vs. control 64 ± 5 mmHg, p < 0.05), maximum dP/dt (3024 ± 266 vs. 1907 ± 360 mmHg/sec, p < 0.05), maximum dV/dt (133 ± 20 vs. 84 ± 6 μL/sec, p < 0.05), and LV border zone wall thickness (1.98 ± 0.06 vs. 1.53 ± 0.07 mm, p < 0.005). Angiogenesis was enhanced (151 ± 10.0 vs. 90 ± 4.5 endothelial cells/hpf, p < 0.005) and apoptosis was reduced (3.9 ± 0.3 vs. 8.2 ± 0.5%, p < 0.005). Increased expression of HGF and Bcl-2 protein was observed in the Adeno-HGF-treated group. Conclusions: Overexpression of HGF 3 weeks post-MI resulted in enhanced angiogenesis, reduced apoptosis, greater preservation of ventricular geometry, and preservation of cardiac contractile function. This technique may be useful to treat or prevent postinfarction heart failure.
AB - Background: Heart failure following myocardial infarction (MI) is a significant cause of morbidity and mortality and remains a difficult therapeutic challenge. Hepatocyte growth factor (HGF) is a potent angiogenic and anti-apoptotic protein whose receptor is upregulated following MI. This study was designed to investigate the ability of HGF to prevent heart failure in a rat model of experimental MI. Methods: The rats underwent direct intramyocardial injection with replication-deficient adenovirus encoding HGF (n = 7) or null virus as control (n = 7) 3 weeks following ligation of the left anterior descending coronary artery. Analysis of the following was performed 3 weeks after injection: cardiac function by pressure-volume conductance catheter measurements; LV wall thickness; angiogenesis by Von Willebrand's factor staining; and apoptosis by the TUNEL assay. The expression levels of HGF and the anti-apoptotic factor Bcl-2 were analyzed by Western blot. Results: Adeno-HGF-treated animals had greater preservation of maximum LV pressure (HGF 77 ± 3 vs. control 64 ± 5 mmHg, p < 0.05), maximum dP/dt (3024 ± 266 vs. 1907 ± 360 mmHg/sec, p < 0.05), maximum dV/dt (133 ± 20 vs. 84 ± 6 μL/sec, p < 0.05), and LV border zone wall thickness (1.98 ± 0.06 vs. 1.53 ± 0.07 mm, p < 0.005). Angiogenesis was enhanced (151 ± 10.0 vs. 90 ± 4.5 endothelial cells/hpf, p < 0.005) and apoptosis was reduced (3.9 ± 0.3 vs. 8.2 ± 0.5%, p < 0.005). Increased expression of HGF and Bcl-2 protein was observed in the Adeno-HGF-treated group. Conclusions: Overexpression of HGF 3 weeks post-MI resulted in enhanced angiogenesis, reduced apoptosis, greater preservation of ventricular geometry, and preservation of cardiac contractile function. This technique may be useful to treat or prevent postinfarction heart failure.
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U2 - 10.1111/j.0886-0440.2005.200373.x
DO - 10.1111/j.0886-0440.2005.200373.x
M3 - Article
C2 - 15673421
AN - SCOPUS:12944265531
SN - 0886-0440
VL - 20
SP - 93
EP - 101
JO - Journal of Cardiac Surgery
JF - Journal of Cardiac Surgery
IS - 1
ER -