The efficacy of a ‘master switch gene’ HIF-1α in a porcine model of chronic myocardial ischaemia

Heinl-Green, Amanda; Radke, Peter W.; Munkonge, Felix M.; Frass, Oliver M.; Zhu, Jie; Vincent, Karen A.; Geddes, Duncan M.; Alton, Eric W.F.W.

doi:10.1093/eurheartj/ehi223

Cited by 40 publications

(32 citation statements)

References 18 publications

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“…Shyu et al (2002) found that HIF-1␣/VP16 reduces infarct size and increases collateral vessel formation in myocardial tissue from rats after acute myocardial infarction (Shyu et al, 2002). A more recent study using an in vivo porcine model of chronic myocardial ischemia demonstrated significant improvement in myocardial perfusion and postischemic left ventricular dysfunction (Heinl-Green et al, 2005). The current study by Luo et al (2006) supports the idea that HIF-1␣/VP16 is capable of up-regulating BNP in cardiomyocytes (Luo et al, 2006).…”

Section: Hif Transcription Factorssupporting

confidence: 70%

Potential Therapeutic Gene for the Treatment of Ischemic Disease: Ad2/Hypoxia-Inducible Factor-1α (HIF-1)/VP16 Enhances B-Type Natriuretic Peptide Gene Expression via a HIF-1-Responsive Element

Wilhide¹,

Jones²

2006

Mol Pharmacol

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In this issue of Molecular Pharmacology, Luo et al. (p. 1953) present a study employing a HIF-1␣/VP16 chimera to investigate the mechanism by which this constitutively active transcription factor activates expression of brain natriuretic peptide (BNP). The results define a functional hypoxia responsive element (HRE) in the promoter of the human BNP gene and demonstrate that this HRE is necessary for HIF-1␣/VP16-induced gene expression in human cardiomyocytes grown under normoxic conditions. Luo et al. also show that a consensus E-box DNA binding sequence is necessary for appropriate BNP

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Section: Hif Transcription Factorssupporting

confidence: 70%

Potential Therapeutic Gene for the Treatment of Ischemic Disease: Ad2/Hypoxia-Inducible Factor-1α (HIF-1)/VP16 Enhances B-Type Natriuretic Peptide Gene Expression via a HIF-1-Responsive Element

Wilhide¹,

Jones²

2006

Mol Pharmacol

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“…This HIF-1␣͞VP16 construct has been shown to induce improved perfusion in ischemia models in the rabbit hindlimb (17). In porcine models of myocardial ischemia, HIV-1␣͞VP16 induced improved perfusion and left ventricular function when delivered with an adenoviral vector but not by naked plasmid DNA (18). In skeletal muscle, HIF-1␣͞VP16 was shown to induce a more mature angiogeneic response compared with VEGF when DNA encoding either one was administered with an adeno-associated virus vector (19).…”

mentioning

confidence: 97%

Peptide-matrix-mediated gene transfer of an oxygen-insensitive hypoxia-inducible factor-1α variant for local induction of angiogenesis

Trentin

Hall

Wechsler

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

124

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“…Similarly, in a porcine model of chronic myocardial ischemia, 21 Ad2HIF over a concentration range from 10 8 to 10 10 viral particles (VP), showed significantly improved perfusion and improved ventricular function after 4 weeks.…”

Section: Modified Hypoxia-inducible Factor (Hif)-1α Transcriptionmentioning

confidence: 98%

Myocardial Transfection of Hypoxia Inducible Factor-1.ALPHA. via an Adenoviral Vector During Coronary Artery Bypass Grafting - A Multicenter Phase I and Safety Study -

Kilian¹,

Sadoni²,

Vicol³

et al. 2010

Circ J

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Background:Increasing numbers of patients with advanced coronary artery disease have limited options for percutaneous and/or surgical revascularization. A prospective, randomized, phase I clinical multicenter trial was performed to assess the feasibility and safety of delivering a pro-angiogenic transcription factor termed "hypoxia inducible factor-1α", delivered to ischemic cardiac muscle via a type 2 adenoviral (Ad2HIF) vector. Methods and Results:The 13 patients were included under the following criteria: 1 hypoperfused area of viable ventricular muscle without options for revascularization and left ventricular ejection fraction ≥30%. After coronary artery bypass grafting was completed, 10 injections of the study drug (n=10), in 3 escalating doses up to 1×10 11 viral particles or saline (n=3) as a placebo control, were injected intramyocardially. After completion of the 1-year follow-up, all patients had uncomplicated postoperative courses, are alive and feeling well; 1 patient had a self-limited run of tachycardia postoperatively and at 6 months, 1 patient developed recurrent angina. Positron emission tomography perfusion analysis revealed improvement in the Ad2HIF injected areas in selected patients. Conclusions:These data support the feasibility and preliminary safety of adenoviral transfection with Ad2HIF in regions of viable myocardium. Additional studies will be required to determine the efficacy and safety of Ad2HIF. (Circ J 2010; 74: 916 - 924)

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The efficacy of a ‘master switch gene’ HIF-1α in a porcine model of chronic myocardial ischaemia

Abstract: Ad2/HIF-1alpha increased myocardial perfusion and improved LV function. Plasmid HIF-1alpha was not associated with improvements in any bioactivity endpoints.

Cited by 40 publications

References 18 publications

Potential Therapeutic Gene for the Treatment of Ischemic Disease: Ad2/Hypoxia-Inducible Factor-1α (HIF-1)/VP16 Enhances B-Type Natriuretic Peptide Gene Expression via a HIF-1-Responsive Element

Potential Therapeutic Gene for the Treatment of Ischemic Disease: Ad2/Hypoxia-Inducible Factor-1α (HIF-1)/VP16 Enhances B-Type Natriuretic Peptide Gene Expression via a HIF-1-Responsive Element

Peptide-matrix-mediated gene transfer of an oxygen-insensitive hypoxia-inducible factor-1α variant for local induction of angiogenesis

Myocardial Transfection of Hypoxia Inducible Factor-1.ALPHA. via an Adenoviral Vector During Coronary Artery Bypass Grafting - A Multicenter Phase I and Safety Study -

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