Gene therapy for chronic myocardial ischemia using platelet-derived endothelial cell growth factor in dogs

Abstract

therapy for chronic myocardial ischemia using platelet-derived endothelial cell growth factor in dogs.

Thymidine Phosphorylase Gene Transfer Inhibits Vascular Smooth Muscle Cell Proliferation by Upregulating Heme Oxygenase-1 and p27 KIP1

“…3,4 Although TP/PD-ECGF has no mitogenic effect on endothelial cells, such as that of vascular endothelial growth factor, Sengupta et al reported that equimolar concentrations of TP/PD-ECGF and vascular endothelial growth factor induce similar monolayer recovery in wounded endothelium. 8 Taking these observations together with our previous in vivo study into account, 9 we believe that TP/PD-ECGF has a strong angiogenic effect. However, the effect of TP/PD-ECGF on other types of vascular cells, especially VSMCs, required further consideration.…”

“…[5][6][7][8] In our previous study using the TP/PD-ECGF gene to alleviate myocardial ischemia in vivo, therapeutic effects involved the induction of angiogenesis including arteriogenesis, as well as decreased myocardial apoptosis, although downstream signals and molecular mechanisms underlying these effects remain obscure. 9 In contrast, the effects of TP on VSMCs should not be neglected, because VSMCs are involved in neointima formation in the setting of vascular disease, arteriogenesis, and vessel maturation after angiogenesis. 10,11 HO-1, also known as heat shock protein (HSP) 32, can be expressed in essentially any tissue on appropriate stimulation, and plays a physiological role in the vasculature because of its antiatherogenic properties.…”

Plasmid-mediated VEGF gene transfer induces cardiomyogenesis and reduces myocardial infarct size in sheep

“…Most studies on the effect of transfection of genes encoding for angiogenic growth factors on experimental AMI have been made in rodents [12][13][14][15][16][17] and only a few in large mammals. Moreover, the latter studies have used a model of chronic ischemia rather than AMI, 18 or assessed variables other than infarct size. 19 When selecting a large mammalian model of AMI we chose the sheep because, unlike pigs, whose cardiomyocytes have up to 32 nuclei, 1,2 ovine cardiomyocytes have only 1-4 nuclei, thus being more similar to human.…”

Development and evaluation of canine reference genes for accurate quantification of gene expression

“…Recently, the dog became a model organism in translational physiology to bridge rodent models to human medicine. Examples include cardiovascular diseases [1], hematopoietic diseases [2,3], and copper storage diseases such as Wilson's disease [4]. In some cases, the genetic defect has been found in dogs first and in humans only later [5].…”