Therapeutic angiogenesis using naked DNA expressing two isoforms of the hepatocyte growth factor in a porcine acute myocardial infarction model☆

Abstract

Intramyocardial injection of pCK-HGF-X7 induced significant angiogenesis at infarct-border zone, and increased the left ventricular stroke volume probably caused by reverse remodeling process.

Naked DNA expressing two isoforms of hepatocyte growth factor induces collateral artery augmentation in a rabbit model of limb ischemia

“…The data presented in this report are consistent with previous results showing the improvement by pCK-HGF-X7 of the myocardial perfusion, viability and left ventricular function, as measured by magnetic resonance imaging 28,29 and 99mTc-methoxyisobutylisonitrile Single Photon Emission Computed Tomography 30 in the porcine heart disease model.…”

Safety of a non-viral plasmid-encoding dual isoforms of hepatocyte growth factor in critical limb ischemia patients: a phase I study

“…12,15,31 The key feature of HGF-X7 is that it was designed by inserting the truncated intron 4 into the junction between exon 4 and exon 5 of hgf cDNA, so that both isoforms of HGF protein are expressed simultaneously and efficiently as in the human genome. 15 Because there is no change in the coding region of the hgf gene, HGF proteins generated from VM202 are identical to the wild-type human HGF proteins.…”

“…9,10 In addition, a phase II, placebo-controlled trial using a single isoform of hepatocyte growth factor (HGF), an angiogenic protein that regulates multiple genes involved in the angiogenic process in patients with CLI, demonstrated excellent safety with an increase in transcutaneous oxygen tension (TCPO 2 ) in the high-dose group, thus providing evidence for its bioactivity. 11 VM202, a DNA plasmid that contains a novel genomic cDNA hybrid of human hgf gene expressing two wild-type isoforms of HGF (pCK-HGF-X7), has been shown in porcine myocardial infarction models to improve myocardial perfusion and left-ventricular function, 12,13 as well as increased capillaries, improved myocardial viability and left-ventricular function compared with control animals. 14 Moreover, in a rabbit hindlimb model, investigators found that co-expression of both isoforms of HGF could more efficiently induce the migration of HUVEC and C 2 C 12 myoblasts than VEGF 165 or single isoform of HGF.…”

Cardiac Vasculature: Development and Pathology

“…(Lee et al, 2003;Su et al, 2002) and the treated animals have reduced infarct size and increased angiogenesis (Dong et al, 2009;Yockman et al, 2009). Hepatocyte growth factor gene therapy: Human Hepatocyte Growth Factor (hHGF) gene therapy induced angiogenesis in rats and dogs after experimental myocardial infarction (MI) and also improved cardiac function (Ahmet et al, 2002;Ahmet et al, 2003;Cho et al, 2008;Jayasankar et al, 2003;Jin et al, 2004;Li et al, 2003;Taniyama et al, 2002;Yang et al, 2007;Yang et al, 2010). HGF gene therapy combined with a novel gene transfection strategy that looks promising in a rat model of MI (Ahmet et al, 2003) is currently being evaluated in clinical trials.…”