Gene Therapy for Myocardial Protection : Transfection of Donor Hearts With Heat Shock Protein 70 Gene Protects Cardiac Function Against Ischemia-Reperfusion Injury

Jayakumar, Jay; Suzuki, Ken; Khan, Muhammad; Smoleński, Ryszard T.; Farrell, Aldo; Latif, Najma; Raisky, Olivier; Abunasra, Haitham; Sammut, Ivan A.; Murtuza, Bari; Amrani, Mohamed; Yacoub, Magdi H.

doi:10.1161/01.cir.102.suppl_3.iii-302

Cited by 54 publications

(47 citation statements)

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“…Glucose-insulin-potassium infusion improves the survival of patients with ischemic heart disease, partially because of enhanced glucose uptake and glycolysis by the ischemic myocardium (1). Studies in transgenic mice overexpressing HSP70 and in rats that had received HSP70 expression vectors also indicate that this protein protects myocardium against ischemiareperfusion injury (17,24,26,29,31). Recently we reported (18) that in human fetal cardiac cells, adenovirus-mediated expression of HIF-1␣/VP16 upregulated VEGF, Glut-1, Glut-3, IGFBP-3, gp130, survivin, TNF-␣-inducible protein, and glycolytic enzymes.…”

Section: Fig 1 Effects Of Preconditioning (Pc) On Cell Viability (Amentioning

confidence: 99%

Expression of constitutively stable hybrid hypoxia-inducible factor-1α protects cultured rat cardiomyocytes against simulated ischemia-reperfusion injury

Date¹,

Mochizuki²,

Belanger³

et al. 2005

American Journal of Physiology-Cell Physiology

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Section: Fig 1 Effects Of Preconditioning (Pc) On Cell Viability (Amentioning

confidence: 99%

Expression of constitutively stable hybrid hypoxia-inducible factor-1α protects cultured rat cardiomyocytes against simulated ischemia-reperfusion injury

Date¹,

Mochizuki²,

Belanger³

et al. 2005

American Journal of Physiology-Cell Physiology

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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%

“…Implantation of stem cells transfected with adrenomedullin was observed to both increase the lifetime of the stem cells and significantly improve overall myocardial function [50]. Lipid-mediated Heat shock protein (HSP70) Jayakumar [43] Lipid-mediated Heat shock protein (HSP70) Jayakumar [44] Naked plasmid…”

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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“…Since all vascular interventions expose the vessel to an ischemic insult, another approach to improving EC function is to protect the endothelium against ischemia/reperfusion injury through the transfection of heat shock proteins. These proteins have been shown to be important in the regulation of normal vessel tone and beneficial in cardiac myocytes [127,128].…”

Section: Ec Gene Therapy To Limit Underlying Smc Proliferationmentioning

confidence: 99%

Cardiovascular gene delivery: The good road is awaiting☆

Brewster

Brey

Greisler

2006

Advanced Drug Delivery Reviews

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Atherosclerotic cardiovascular disease is a leading cause of death worldwide. Despite recent improvements in medical, operative, and endovascular treatments, the number of interventions performed annually continues to increase. Unfortunately, the durability of these interventions is limited acutely by thrombotic complications and later by myointimal hyperplasia followed by progression of atherosclerotic disease over time. Despite improving medical management of patients with atherosclerotic disease, these complications appear to be persisting. Cardiovascular gene therapy has the potential to make significant clinical inroads to limit these complications. This article will review the technical aspects of cardiovascular gene therapy; its application for promoting a functional endothelium, smooth muscle cell growth inhibition, therapeutic angiogenesis, tissue engineered vascular conduits, and discuss the current status of various applicable clinical trials.

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Gene Therapy for Myocardial Protection : Transfection of Donor Hearts With Heat Shock Protein 70 Gene Protects Cardiac Function Against Ischemia-Reperfusion Injury

Cited by 54 publications

References 0 publications

Expression of constitutively stable hybrid hypoxia-inducible factor-1α protects cultured rat cardiomyocytes against simulated ischemia-reperfusion injury

Expression of constitutively stable hybrid hypoxia-inducible factor-1α protects cultured rat cardiomyocytes against simulated ischemia-reperfusion injury

Non‐viral gene therapy for myocardial engineering

Cardiovascular gene delivery: The good road is awaiting☆

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