Induction of Angiogenesis and Inhibition of Apoptosis by Hepatocyte Growth Factor Effectively Treats Postischemic Heart Failure

Jayasankar, Vasant; Woo, Y. Joseph; Pirolli, Timothy J.; Bish, T.; Berry, Mark F.; Burdick, Jeffrey; Gardner, Timothy J.; Sweeney, H. Lee

doi:10.1111/j.0886-0440.2005.200373.x

Cited by 82 publications

(61 citation statements)

References 35 publications

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“…Apoptotic cardiomyocyte loss after infarction is also known to be variable, and its severity and extent can be modulated by several pathophysiological mechanisms and variables, such as the renin-angiotensin-aldosterone system or adrenergic stimulation [13][14]. In an experimental animal model, the administration of anti-apoptotic protein (hepatocyte growth factor) was associated with decreased apoptosis and left ventricular remodeling [15]. Clinical studies seem to suggest that the pharmacological benefits of ACE inhibition and b-adrenergic receptor blockade, in human heart failure, are at least partly attributable to interruption of apoptosis [16][17].…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of TNF-Related Apoptosis Inducing Ligand (TRAIL) in acute coronary syndrome patients

Osmančík

Toušek

Teringová

et al. 2013

European Heart Journal

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Section: Discussionmentioning

confidence: 99%

Prognostic value of TNF-Related Apoptosis Inducing Ligand (TRAIL) in acute coronary syndrome patients

Osmančík

Toušek

Teringová

et al. 2013

European Heart Journal

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“…VM202 is not only a potent angiogenic and anti-apoptotic agent, 26,27 but may also function as a neurotrophic factor, capable of promoting axonal growth and regeneration. 28 As loss of microvasculature in diabetes has also been implicated in acceleration of neuronal loss and pain symptoms, 29 VM202 may be an ideally suited candidate for the treatment of patients with diabetes or neuropathy.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2011

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We aimed to evaluate in a phase I dose-escalation study, the safety of intramuscular injections of a novel non-viral plasmid DNA expressing two isoforms of human hepatocyte growth factor (HGF) (VM202) in patients with critical limb ischemia (CLI). In total, 12 patients with CLI and unsuitable for revascularization were consecutively assigned to increasing doses (2 to 16 mg) of VM202 administered into the ischemic calf muscle at days 1 and 15. Patients were evaluated for safety and tolerability, changes in ankle-and toe brachial index (ABI and TBI), and pain severity score using a visual analog scale (VAS) throughout a 12-month follow-up period. Median age was 72 years and 53% of the patients were male. VM202 was safe and well tolerated with no death during the 12-month follow-up. Median ABI and TBI significantly increased from 0.35 to 0.52 (P¼0.005) and from 0.15 to 0.24 (P¼0.01) at 12 months follow-up. Median VAS decreased from 57.5 to 16.0 mm at 6 months follow-up (P¼0.03). In this first human clinical trial, VM202, which expresses two isoforms of human HGF, appear to be safe and well tolerated with encouraging clinical results and thus supports the performance of a phase II randomized controlled trial.

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“…34 Infarct extent (%) was calculated as infarct circumference divided by LV circumference Â 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.…”

Section: Animal Surgerymentioning

confidence: 99%

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

Jin¹,

Inubushi²,

Masamoto

et al. 2011

Gene Ther

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We investigated the long-term effects of human hepatocyte growth factor (HGF) gene therapy in a rat myocardial infarct model. Treatment adenovirus coexpressing the HGF therapeutic gene and the human sodium/iodide symporter (NIS) reporter gene or control adenovirus expressing the NIS gene alone were injected directly into the infarct border zone immediately after permanent coronary ligation in rats (n ¼ 6 each). A uniform disease state was confirmed in the acute phase in terms of impaired left ventricular (LV) function by cine magnetic resonance imaging (MRI), large infarct extent by 99m Tc-tetrofosmin single-photon emission computed tomography (SPECT) and successful gene transfer and expression by 99m TcO 4 À SPECT. After a 10-week follow-up, repeated cine MRI demonstrated no significant difference in the LV ejection fraction between the time points or groups, but a significantly increased end-diastolic volume from the acute to the chronic phase without a significant difference between the groups. Capillary density was significantly higher in the treatment group, whereas arteriole density remained unchanged. Two-photon excitation fluorescence microscopy revealed extremely thin capillaries (2--5 mm), and their irregular networks increased in the infarct border zone of the treated myocardium. Our results indicated that single HGF gene therapy alone induced an immature and irregular microvasculature.

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Induction of Angiogenesis and Inhibition of Apoptosis by Hepatocyte Growth Factor Effectively Treats Postischemic Heart Failure

Abstract: 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.

Cited by 82 publications

References 35 publications

Prognostic value of TNF-Related Apoptosis Inducing Ligand (TRAIL) in acute coronary syndrome patients

Prognostic value of TNF-Related Apoptosis Inducing Ligand (TRAIL) in acute coronary syndrome patients

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

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

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