2009
DOI: 10.1002/jgm.1318
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A hypoxic inducible factor‐1α hybrid enhances collateral development and reduces vascular leakage in diabetic rats

Abstract: The endogenous angiogenic response to ischemia was impaired in ZDF rats, possibly due to down-regulation of angiogenic factors. Ad2/HIF-1 alpha/VP16 enhanced collateral development and reduced vascular leakage in the ischemic hindlimb of ZDF rats indicating that hybrid HIF-1 alpha angiogenic therapy may be efficacious for peripheral vascular disease with a diabetic comorbidity.

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Cited by 25 publications
(19 citation statements)
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“…1B) 36, 37. Experimental results demonstrating that the impairment of HIF-1α transactivation was maintained even when constitutive HIF-1α protein was overexpressed and when CTAD was unaffected by high glucose exposure supported this conclusion.…”
Section: The Negative Effects Of Methylglyoxalmentioning
confidence: 78%
See 2 more Smart Citations
“…1B) 36, 37. Experimental results demonstrating that the impairment of HIF-1α transactivation was maintained even when constitutive HIF-1α protein was overexpressed and when CTAD was unaffected by high glucose exposure supported this conclusion.…”
Section: The Negative Effects Of Methylglyoxalmentioning
confidence: 78%
“…Experimental results demonstrating that the impairment of HIF-1α transactivation was maintained even when constitutive HIF-1α protein was overexpressed and when CTAD was unaffected by high glucose exposure supported this conclusion. The mutation of arginine 354 (Arg-354) of p300 prevented the modification of p300 and rescued its interaction with HIF-1α 36, 37. High glucose-induced decreases in transactivation of HIF-1 led to impaired VEGF production in response to hypoxia, which resulted in reduced neovascularization in cells obtained from diabetic patients and impaired wound healing in ischemic diabetic animals 36, 37.…”
Section: The Negative Effects Of Methylglyoxalmentioning
confidence: 99%
See 1 more Smart Citation
“…116,133,135,164 Consistent with this finding, adenoviral delivery of an O 2 -refractory form of HIF-1α exhibited benefit in limb ischemia models in aged and diabetic mice. 116,129,165 A similar approach, treatment with DNA encoding the N-terminus of HIF-1α fused to the VP16 transactivation domain, also stimulated angiogenesis in animal models [166][167][168] and is currently progressing through phase I and II clinical studies in patients with severe PAD. 169 These approaches, however, suffer from many of the challenges common to gene therapy and must be cautiously evaluated.…”
Section: Monographsmentioning
confidence: 99%
“…Not to underscore polymorphisms in the BNP gene, under the control of the hypoxia-inducible factor, might account for part of variability in BNP response. 37 Also, no detailed cardiovascular fitness assessment was conducted before departure. This could have provided comparative data at a similar workload than that reached at HA, in the absence of which the effects of altitude on our study end points cannot be definitively determined.…”
Section: Limitationsmentioning
confidence: 99%