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Mendeley readers
Attention Score in Context
| Title |
Protection of Blood Retinal Barrier and Systemic Vasculature by Insulin-Like Growth Factor Binding Protein-3
|
|---|---|
| Published in |
PLOS ONE, July 2012
|
| DOI | 10.1371/journal.pone.0039398 |
| Pubmed ID | |
| Authors |
Yagna P. R. Jarajapu, Jun Cai, Yuanqing Yan, Sergio Li Calzi, Jennifer L. Kielczewski, Ping Hu, Lynn C. Shaw, Sue M. Firth, Tailoi Chan-Ling, Michael E. Boulton, Robert C. Baxter, Maria B. Grant |
| Abstract |
Previously, we showed that insulin growth factor (IGF)-1 binding protein-3 (IGFBP-3), independent of IGF-1, reduces pathological angiogenesis in a mouse model of the oxygen-induced retinopathy (OIR). The current study evaluates novel endothelium-dependent functions of IGFBP-3 including blood retinal barrier (BRB) integrity and vasorelaxation. To evaluate vascular barrier function, either plasmid expressing IGFBP-3 under the regulation of an endothelial-specific promoter or a control plasmid was injected into the vitreous humor of mouse pups (P1) and compared to the non-injected eyes of the same pups undergoing standard OIR protocol. Prior to sacrifice, the mice were given an injection of horseradish peroxidase (HRP). IGFBP-3 plasmid-injected eyes displayed near-normal vessel morphology and enhanced vascular barrier function. Further, in vitro IGFBP-3 protects retinal endothelial cells from VEGF-induced loss of junctional integrity by antagonizing the dissociation of the junctional complexes. To assess the vasodilatory effects of IGFBP-3, rat posterior cerebral arteries were examined in vitro. Intraluminal IGFBP-3 decreased both pressure- and serotonin-induced constrictions by stimulating nitric oxide (NO) release that were blocked by L-NAME or scavenger receptor-B1 neutralizing antibody (SRB1-Ab). Both wild-type and IGF-1-nonbinding mutant IGFBP-3 (IGFBP-3NB) stimulated eNOS activity/NO release to a similar extent in human microvascular endothelial cells (HMVECs). NO release was neither associated with an increase in intracellular calcium nor decreased by Ca(2+)/calmodulin-dependent protein kinase II (CamKII) blockade; however, dephosphorylation of eNOS-Thr(495) was observed. Phosphatidylinositol 3-kinase (PI3K) activity and Akt-Ser(473) phosphorylation were both increased by IGFBP-3 and selectively blocked by the SRB1-Ab or PI3K blocker LY294002. In conclusion, IGFBP-3 mediates protective effects on BRB integrity and mediates robust NO release to stimulate vasorelaxation via activation of SRB1. This response is IGF-1- and calcium-independent, but requires PI3K/Akt activation, suggesting that IGFBP-3 has novel protective effects on retinal and systemic vasculature and may be a therapeutic candidate for ocular complications such as diabetic retinopathy. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 45 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 45 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 9 | 20% |
| Researcher | 6 | 13% |
| Student > Ph. D. Student | 6 | 13% |
| Professor | 5 | 11% |
| Student > Doctoral Student | 3 | 7% |
| Other | 6 | 13% |
| Unknown | 10 | 22% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 12 | 27% |
| Agricultural and Biological Sciences | 7 | 16% |
| Biochemistry, Genetics and Molecular Biology | 5 | 11% |
| Neuroscience | 4 | 9% |
| Unspecified | 1 | 2% |
| Other | 5 | 11% |
| Unknown | 11 | 24% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. 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 14 July 2012.
All research outputs
#20,161,674
of 22,671,366 outputs
Outputs from PLOS ONE
#172,677
of 193,517 outputs
Outputs of similar age
#148,004
of 164,299 outputs
Outputs of similar age from PLOS ONE
#3,638
of 3,977 outputs
Altmetric has tracked 22,671,366 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 193,517 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.0. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 3,977 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.