A hypoxic inducible factor‐1α hybrid enhances collateral development and reduces vascular leakage in diabetic rats

Kajiwara, Hiroyuki; Luo, Zhengyu; Belanger, Adam J.; Urabe, Akihiro; Vincent, Karen A.; Akita, Geoffrey Y.; Cheng, Seng H.; Mochizuki, Seibu; Gregory, Richard J.; Jiang, Canwen

doi:10.1002/jgm.1318

Cited by 25 publications

(17 citation statements)

References 39 publications

(80 reference 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%

“…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%

“…Kajiwara et al demonstrated that the usage of adenoviral vectors expressing a constitutively active HIF-1α hybrid (Ad2/HIF-1α/VP16) increased collateral development in a diabetic rat model 36. Delivery of AdCA5 (an adenovirus encoding a constitutively active form of HIF-1α) was effective in blocking hyperglycemia-reduced VEGF protein expression and ameliorating maternal diabetes-induced embryonic vasculopathy 74.…”

Section: Possible Therapiesmentioning

confidence: 99%

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The Possible Mechanisms Underlying the Impairment of HIF-1α Pathway Signaling in Hyperglycemia and the Beneficial Effects of Certain Therapies

Xiao¹,

Gu²,

Wang³

et al. 2013

Int. J. Med. Sci.

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Hypoxia-inducible factor 1 alpha (HIF-1α), an essential transcription factor which mediates the adaptation of cells to low oxygen tensions, is regulated precisely by hypoxia and hyperglycemia, which are major determinants of the chronic complications associated with diabetes. The process of HIF-1α stabilization by hypoxia is clear; however, the mechanisms underlying the potential deleterious effect of hyperglycemia on HIF-1α are still controversial, despite reports of a variety of studies demonstrating the existence of this phenomenon. In fact, HIF-1α and glucose can sometimes influence each other: HIF-1α induces the expression of glycolytic enzymes and glucose metabolism affects HIF-1α accumulation in some cells. Although hyperglycemia upregulates HIF-1α signaling in some specific cell types, we emphasize the inhibition of HIF-1α by high glucose in this review. With regard to the mechanisms of HIF-1α impairment, the role of methylglyoxal in impairment of HIF-1α stabilization and transactivation ability and the negative effect of reactive oxygen species (ROS) on HIF-1α are discussed. Other explanations for the inhibition of HIF-1α by high glucose exist: the increased sensitivity of HIF-1α to Von Hippel-Lindau (VHL) machinery, the role of osmolarity and proteasome activity, and the participation of several molecules. This review aims to summarize several important developments regarding these mechanisms and to discuss potentially effective therapeutic techniques (antioxidants eicosapentaenoic acid (EPA) and metallothioneins (MTs), pharmaceuticals cobalt chloride (CoCl2), dimethyloxalylglycine (DMOG), desferrioxamine (DFO) and gene transfer of constitutively active forms of HIF-1α) and their mechanisms of action for intervention in the chronic complications in diabetes.

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Section: The Negative Effects Of Methylglyoxalmentioning

confidence: 78%

Section: The Negative Effects Of Methylglyoxalmentioning

confidence: 99%

Section: Possible Therapiesmentioning

confidence: 99%

See 1 more Smart Citation

The Possible Mechanisms Underlying the Impairment of HIF-1α Pathway Signaling in Hyperglycemia and the Beneficial Effects of Certain Therapies

Xiao¹,

Gu²,

Wang³

et al. 2013

Int. J. Med. Sci.

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“…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%

Hypoxia-Induced Angiogenesis: Good and Evil

2011

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The vascular network delivers oxygen (O 2 ) and nutrients to all cells within the body. It is therefore not surprising that O 2 availability serves as a primary regulator of this complex organ. Most transcriptional responses to low O 2 are mediated by hypoxia-inducible factors (HIFs), highly conserved transcription factors that control the expression of numerous angiogenic, metabolic, and cell cycle genes. Accordingly, the HIF pathway is currently viewed as a master regulator of angiogenesis. HIF modulation could provide therapeutic benefit for a wide array of pathologies, including cancer, ischemic heart disease, peripheral artery disease, wound healing, and neovascular eye diseases. Hypoxia promotes vessel growth by upregulating multiple pro-angiogenic pathways that mediate key aspects of endothelial, stromal, and vascular support cell biology. Interestingly, recent studies show that hypoxia influences additional aspects of angiogenesis, including vessel patterning, maturation, and function. Through extensive research, the integral role of hypoxia and HIF signaling in human disease is becoming increasingly clear. Consequently, a thorough understanding of how hypoxia regulates angiogenesis through an ever-expanding number of pathways in multiple cell types will be essential for the identification of new therapeutic targets and modalities.

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“…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%

Brain Natriuretic Peptide Levels and the Occurrence of Subclinical Pulmonary Edema in Healthy Lowlanders at High Altitude

Pagé

Henri

Pagé

et al. 2015

Canadian Journal of Cardiology

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A hypoxic inducible factor‐1α hybrid enhances collateral development and reduces vascular leakage in diabetic rats

Cited by 25 publications

References 39 publications

The Possible Mechanisms Underlying the Impairment of HIF-1α Pathway Signaling in Hyperglycemia and the Beneficial Effects of Certain Therapies

The Possible Mechanisms Underlying the Impairment of HIF-1α Pathway Signaling in Hyperglycemia and the Beneficial Effects of Certain Therapies

Hypoxia-Induced Angiogenesis: Good and Evil

Brain Natriuretic Peptide Levels and the Occurrence of Subclinical Pulmonary Edema in Healthy Lowlanders at High Altitude

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