Gene Transfer of Hepatocyte Growth Factor Attenuates Postinfarction Heart Failure

Abstract

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 (nϭ10) or empty null virus as control (nϭ9)

Administration of Pigment Epithelium-Derived Factor Inhibits Left Ventricular Remodeling and Improves Cardiac Function in Rats with Acute Myocardial Infarction

“…37,38 In the present study, PEDF administration not only inhibited LV dilatation and anterior wall thickness thinning but also suppressed LV remodeling evaluated by LV mass index and improved cardiac systolic and diastolic function at 8 weeks after AMI (Table 1). Attenuated collagen deposition in the remodeling myocardium could explain decreased diastolic dysfunction but is not necessarily responsible for reduced dilative remodeling in PEDF-treated animals.…”

“…6 -8,35,36 In addition, apoptotic cell death in and around the region of myocardial infarction is reported to contribute to the process of cardiac fibrosis and LV remodeling in AMI. 37,38 These observations suggest that PEDF could inhibit cardiac fibrosis and LV remodeling after AMI partly by inhibiting apoptotic cell death of cardiomyocytes via suppression of oxidative stress generation in noninfarcted LV areas. In this study, PEDF administration inhibited TGF-␤ and type III collagen gene expression in noninfarcted LV areas at 8 weeks after AMI ( Figure 6, C and D).…”

Inhibition of Matrix Metalloproteinase Activity by TIMP-1 Gene Transfer Effectively Treats Ischemic Cardiomyopathy

“…This location was standardized for all animals and was highly reproducible given the consistent areas of infarction in this model and the easily identifiable landmarks of the ligation suture and the apex, as we have previously reported. 20 Two sections were obtained from this area, and the diameter and border-zone wall thickness were measured as described in 2 sections and averaged. Measurements were performed on digitized photomicrographs using Openlab image processing software (Improvision) with standards of known length.…”

Long-term effects of hepatocyte growth factor gene therapy in rat myocardial infarct model

“…34 Infarct extent (%) was calculated as infarct circumference divided by LV circumference  100 on a slice with the maximum infarct extent. The border zone wall thickness, which has been reported as a parameter of ventricular remodeling after myocardial infarction, 8,10 was also measured at the center of the infarct border zone consisting of both normal and scar tissues on the same slice. Specimens were also immunostained with platelet/endothelial cell adhesion molecule-1 (sc-1506; Santa Cruz Biotechnology, Santa Cruz, CA, USA) using a goat ABC staining system (sc-2023; Santa Cruz Biotechnology) for capillaries and a-smooth muscle actin immunohistology kit (IMMH2; Sigma-Aldrich) for arterioles, according to the manufacturer's protocols.…”