Gene transfer of hepatocyte growth factor attenuates postinfarction heart failure

Circulation. 2003 Sep 9;108 Suppl 1:II230-6. doi: 10.1161/01.cir.0000087444.53354.66.


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-xL 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Apoptosis
  • Genetic Vectors
  • Heart / physiopathology
  • Heart Failure / etiology
  • Heart Failure / pathology
  • Heart Failure / physiopathology
  • Heart Failure / therapy*
  • Heart Ventricles / pathology
  • Hemodynamics
  • Hepatocyte Growth Factor / analysis
  • Hepatocyte Growth Factor / genetics*
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Male
  • Microspheres
  • Myocardial Infarction / complications*
  • Neovascularization, Physiologic
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Rats, Inbred Lew
  • von Willebrand Factor / analysis
  • von Willebrand Factor / immunology


  • Proto-Oncogene Proteins c-bcl-2
  • von Willebrand Factor
  • Hepatocyte Growth Factor