Gene transfer of hepatocyte growth factor attenuates postinfarction heart failure

被引:85
作者
Jayasankar, V
Woo, YJ
Bish, LT
Pirolli, TJ
Chatterjee, S
Berry, MF
Burdick, J
Gardner, TJ
Sweeney, HL
机构
[1] Univ Penn, Sch Med, Dept Cardiothorac Surg, Div Cardiothorac Surg, Philadelphia, PA 19104 USA
[2] Univ Penn, Sch Med, Dept Physiol, Philadelphia, PA 19104 USA
关键词
angiogenesis; heart failure; gene therapy; apoptosis;
D O I
10.1161/01.cir.0000087444.53354.66
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background-Despite advances in surgical and percutaneous coronary revascularization, ongoing ischemia that is not amenable to standard revascularization techniques is a major cause of morbidity and mortality. Hepatocyte Growth Factor (HGF) has potent angiogenic and anti-apoptotic activities, and this study evaluated the functional and biochemical effects of HGF gene transfer in a rat model of postinfarction heart failure. Methods and Results-Lewis rats underwent ligation of the left anterior descending coronary artery with direct intramyocardial injection of replication-deficient recombinant adenovirus encoding HGF (n=10) or empty null virus as control (n=9), and animals were analyzed after six weeks. Pressure-volume conductance catheter measurements demonstrated significantly preserved contractile function in the HGF group compared with Null control animals as measured by maximum developed LV pressure (79+/-5 versus 56+/-4 mm Hg, P<0.001) and maximum dP/dt (2890 +/- 326 versus 1622 +/- 159 mm Hg/sec, P<0.01). Significant preservation of LV geometry was associated with HGF treatment (LV Diameter HGF 13.1+/-0.54 versus Null 14.4+/-0.15 mm P<0.01; LV wall thickness 1.73 +/- 0.10 versus 1.28 +/- 0.07 mm P<0.01). Angiogenesis was significantly enhanced in HGF treated animals as measured by both Von Willebrand's Factor immunohistochemical staining and a microsphere assay. TUNEL analysis revealed a significant reduction in apoptosis in the HGF group (3.42+/-0.83% versus 8.36+/-1.16%, P<0.01), which correlated with increased Bcl-2 and Bcl-x(L) expression in the HGF animals. Conclusions-Hepatocyte Growth Factor gene transfer following a large myocardial infarction results in significantly preserved myocardial function and geometry, and is associated with significant angiogenesis and a reduction in apoptosis. This therapy may be useful as an adjunct or alternative to standard revascularization techniques in patients with ischemic heart failure.
引用
收藏
页码:230 / 236
页数:7
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