Protection From Ischemic Heart Injury by a Vigilant Heme Oxygenase-1 Plasmid System

Tang, Yao; Tang, Yi; Zhang, Y. Clare; Qian, Keping; Shen, Leping; Phillips, M. Ian

doi:10.1161/01.hyp.0000120152.27263.87

Cited by 70 publications

(61 citation statements)

References 25 publications

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“…18,[33][34][35][36] This notion is in agreement with our recent report that hypoxia-inducible expression of HO-1 conferred significant protection to the heart following myocardial ischemia. 37 The vigilant vector system targets tissue selectively, unlike other HRE-SV40-based gene switch systems which are not tissue selective. Using the ODDbased system in combination with the MLC-2v promoter, we can achieve heart-selective and hypoxia-responsive expression of HO-1 for optimal cardiac protection.…”

Section: Discussionmentioning

confidence: 99%

“…Using the ODDbased system in combination with the MLC-2v promoter, we can achieve heart-selective and hypoxia-responsive expression of HO-1 for optimal cardiac protection. 37 The ultimate goal of this study was to achieve longlasting therapeutic effects by delivering hypoxia-inducible gene expression with recombinant adeno-associated virus (rAAV). To establish the model, we first tested it with AAV-based plasmid.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A hypoxia-inducible vigilant vector system for activating therapeutic genes in ischemia

Tang

Tang²,

Zhang

et al. 2005

Gene Ther

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A hypoxia-inducible vigilant vector system for activating therapeutic genes in ischemia

Tang

Tang²,

Zhang

et al. 2005

Gene Ther

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“…Therefore, the gene that is to be used should be highly expressed in ischemic periods in order to be more effective. The HO-1 gene therapy does not seem to have lasting effect on the myocardial tissue, while the administration together with the SOD gene may lead to adverse reactions (mitochondrial function disruption, CO overproduction) (Tang YL, 2004). A special type of vectors called "vigilant vectors" was developed so as to be activated only in an ischemic environment (Phillips MI, 2002).…”

Section: Ho-1 (Heme Oxygenase 1)mentioning

confidence: 99%

Gene Therapy Targets and the Role of Pharmacogenomics in Heart Failure

Lykouras¹,

Flordellis²,

Dougenis³

2011

Targets in Gene Therapy

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“…The degree of oxidative stress, and hence myocardial damage, depends on the severity of the ischemic period [41]. Reducing IR damage has been attempted via transfection with genes such as heat shock protein 70 [42][43][44], heme oxygenase [45,46] and nuclear factor κB (NFκB) [47]. Antioxidant gene therapy has been attempted with genes like superoxide dismutase (SOD) [48], which were observed to attenuate the damage due to IR injury.…”

Section: Pacemakingmentioning

confidence: 99%

“…Human heme oxygenase-1 (hHO-1) Tang [45] Lipid-mediated cis element decoy against NFkB Sawa [47] Naked plasmid SOD (superoxide dismutase) Palffy [48] Cell-mediated Adrenomedullin (AM) Jo Ji [50] Cell-mediated Adrenomedullin (AM) Nagaya [51] Naked plasmid HIF De Muinck [52] …”

Section: Pacemakingmentioning

confidence: 99%

Non‐viral gene therapy for myocardial engineering

Holladay

O’Brien

Pandit

2010

WIREs Nanomed Nanobiotechnol

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Despite significant advances in surgical and pharmacological techniques, myocardial infarction remains the main cause of morbidity in the developed world because no remedy has been found for the regeneration of infarcted myocardium. Once the blood supply to the area in question is interrupted, the inflammatory cascade, among other mechanisms, results in the damaged tissue becoming a scar. The goals of cardiac gene therapy are essentially to minimize damage, to promote regeneration or some combination thereof. While the vector is, in theory, less important than the gene being delivered, the choice of vector can have a significant impact. Viral therapies can have very high transfection efficiencies, but disadvantages include immunogenicity, retroviralmediated insertional mutagenesis and the expense and difficulty of manufacture. For these reasons, researchers have focused on non-viral gene therapy as an alternative. In this review, naked plasmid delivery, or the delivery of complexed plasmids, and cellmediated gene delivery to the myocardium will be reviewed. Pre-clinical and clinical trials in the cardiac tissue will form the core of the discussion. While unmodified stem cells are sometimes considered therapeutic vectors based on paracrine mechanisms of action basic understanding is limited. Thus, only genetically modified cells will be discussed as cell-mediated gene therapy.Ischemic heart disease, which includes acute damage due to myocardial infarction (MI) and chronic damage due to atherosclerotic narrowing of vessels, accounts for 35% of deaths reported in the United States every year [1]. MI, which is literally the death of cardiac tissue due to lack of 2 oxygen supply, is the result of the occlusion of a coronary artery. Within a few hours of interrupted blood supply, affected cardiomyocytes die. While the body has adaptive mechanisms, such as hypertrophy of the undamaged cardiac muscle and the development of collateral blood supply to minimize the damage, ischemic heart disease remains the most common cause of death in developed countries [2].The delivery of plasmid DNA to the myocardium is a complicated problem as the transfection efficiency of unmodified DNA is quite low, but complexation with agents designed to improve transfection can increase the cytotoxicity of the treatment [3]. Delivery of uncomplexed plasmid DNA is conceptually the simplest gene delivery technique, but these plasmids have extremely low transfection efficiencies in vitro and are not particularly effective in vivo. Compared to viral vectors, transgene expression is almost negligible and the expression time is also very limited [4]. However, there are significant advantages in using plasmids instead of viruses, such as ease of preparation (large and small scale), very low immunogenicity (as there are essentially no protein or membrane components in the plasmid), capacity for long term storage, ease of recombinant manipulation and much larger expression cassettes [4]. A variety of non-viral techniques are available to improve...

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Protection From Ischemic Heart Injury by a Vigilant Heme Oxygenase-1 Plasmid System

Cited by 70 publications

References 25 publications

A hypoxia-inducible vigilant vector system for activating therapeutic genes in ischemia

A hypoxia-inducible vigilant vector system for activating therapeutic genes in ischemia

Gene Therapy Targets and the Role of Pharmacogenomics in Heart Failure

Non‐viral gene therapy for myocardial engineering

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