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The molecular basis for impaired hypoxia-induced VEGF expression in diabetic tissues

Overview of attention for article published in Proceedings of the National Academy of Sciences of the United States of America, July 2009
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (87th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (51st percentile)

Mentioned by

blogs
1 blog
patent
5 patents
f1000
1 research highlight platform

Citations

dimensions_citation
218 Dimensions

Readers on

mendeley
138 Mendeley
citeulike
2 CiteULike
Title
The molecular basis for impaired hypoxia-induced VEGF expression in diabetic tissues
Published in
Proceedings of the National Academy of Sciences of the United States of America, July 2009
DOI 10.1073/pnas.0906670106
Pubmed ID
Authors

H. Thangarajah, D. Yao, E. I. Chang, Y. Shi, L. Jazayeri, I. N. Vial, R. D. Galiano, X.-L. Du, R. Grogan, M. G. Galvez, M. Januszyk, M. Brownlee, G. C. Gurtner

Abstract

Diabetes is associated with poor outcomes following acute vascular occlusive events. This results in part from a failure to form adequate compensatory microvasculature in response to ischemia. Since vascular endothelial growth factor (VEGF) is an essential mediator of neovascularization, we examined whether hypoxic up-regulation of VEGF was impaired in diabetes. Both fibroblasts isolated from type 2 diabetic patients, and normal fibroblasts exposed chronically to high glucose, were defective in their capacity to up-regulate VEGF in response to hypoxia. In vivo, diabetic animals demonstrated an impaired ability to increase VEGF production in response to soft tissue ischemia. This resulted from a high glucose-induced decrease in transactivation by the transcription factor hypoxia-inducible factor-1alpha (HIF-1alpha), which mediates hypoxia-stimulated VEGF expression. Decreased HIF-1alpha functional activity was specifically caused by impaired HIF-1alpha binding to the coactivator p300. We identify covalent modification of p300 by the dicarbonyl metabolite methylglyoxal as being responsible for this decreased association. Administration of deferoxamine abrogated methylglyoxal conjugation, normalizing both HIF-1alpha/p300 interaction and transactivation by HIF-1alpha. In diabetic mice, deferoxamine promoted neovascularization and enhanced wound healing. These findings define molecular defects that underlie impaired VEGF production in diabetic tissues and offer a promising direction for therapeutic intervention.

Mendeley readers

The data shown below were compiled from readership statistics for 138 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 138 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 1 <1%
Unknown 137 99%
Readers by discipline Count As %
Materials Science 1 <1%
Unknown 137 99%

Attention Score in Context

This research output has an Altmetric Attention Score of 10. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 18 July 2017.
All research outputs
#1,385,385
of 12,364,927 outputs
Outputs from Proceedings of the National Academy of Sciences of the United States of America
#20,009
of 77,321 outputs
Outputs of similar age
#18,337
of 145,120 outputs
Outputs of similar age from Proceedings of the National Academy of Sciences of the United States of America
#457
of 949 outputs
Altmetric has tracked 12,364,927 research outputs across all sources so far. Compared to these this one has done well and is in the 88th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 77,321 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 22.1. This one has gotten more attention than average, scoring higher than 74% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 145,120 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 87% of its contemporaries.
We're also able to compare this research output to 949 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 51% of its contemporaries.