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Induction of Angiogenesis and Inhibition of Apoptosis by Hepatocyte Growth Factor Effectively Treats Postischemic Heart Failure
Author(s) -
Jayasankar Vasant,
Woo Y. Joseph,
Pirolli Timothy J.,
Bish Lawrence T.,
Berry Mark F.,
Burdick Jeffrey,
Gardner Timothy J.,
Sweeney H. Lee
Publication year - 2005
Publication title -
journal of cardiac surgery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.428
H-Index - 58
eISSN - 1540-8191
pISSN - 0886-0440
DOI - 10.1111/j.0886-0440.2005.200373.x
Subject(s) - medicine , hepatocyte growth factor , angiogenesis , apoptosis , western blot , tunel assay , vascular endothelial growth factor , von willebrand factor , myocardial infarction , andrology , heart failure , cardiology , endocrinology , platelet , receptor , immunohistochemistry , biology , biochemistry , gene , vegf receptors
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.