| Title |
Vascular Endothelial Growth Factor Isoform-B Stimulates Neurovascular Repair After Ischemic Stroke by Promoting the Function of Pericytes via Vascular Endothelial Growth Factor Receptor-1
|
|---|---|
| Published in |
Molecular Neurobiology, March 2017
|
| DOI | 10.1007/s12035-017-0478-6 |
| Pubmed ID | |
| Authors |
Noëmie Jean LeBlanc, Revathy Guruswamy, Ayman ElAli |
| Abstract |
Ischemic stroke triggers endogenous angiogenic mechanisms, which correlates with longer survival in patients. As such, promoting angiogenesis appears to be a promising approach. Experimental studies investigated mostly the potent angiogenic factor vascular endothelial growth factor isoform-A (VEGF-A). However, VEGF-A increases the risk of destabilizing the brain microvasculature, thus hindering the translation of its usage in clinics. An attractive alternative VEGF isoform-B (VEGF-B) was recently reported to act as a survival factor rather than a potent angiogenic factor. In this study, we investigated the therapeutic potential of VEGF-B in ischemic stroke using different in vivo and in vitro approaches. We showed that the delayed intranasal administration of VEGF-B reduced neuronal damage and inflammation. Unexpectedly, VEGF-B stimulated the formation of stable brain microvasculature within the injured region by promoting the interaction between endothelial cells and pericytes. Our data indicate that the effects of VEGF-B were mediated via its specific receptor VEGF receptor-1 (VEGFR-1) that is predominately expressed in brain pericytes. Importantly, VEGF-B promoted the survival of pericytes, and not brain endothelial cells, by inducing expression of the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) and the main protein involved in energy homeostasis AMP-activated protein kinase α (AMPKα). Moreover, we showed that VEGF-B stimulated the pericytic release of factors stimulating a "reparative angiogenesis" that does not compromise microvasculature stability. Our study unraveled hitherto unknown role of VEGF-B/VEGFR-1 signaling in regulating the function of pericytes. Furthermore, our findings suggest that brain microvasculature stabilization via VEGF-B constitutes a safe therapeutic approach for ischemic stroke. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Canada | 1 | 33% |
| United States | 1 | 33% |
| Unknown | 1 | 33% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 2 | 67% |
| Science communicators (journalists, bloggers, editors) | 1 | 33% |
Mendeley readers
The data shown below were compiled from readership statistics for 33 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Sweden | 1 | 3% |
| Unknown | 32 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 6 | 18% |
| Student > Ph. D. Student | 5 | 15% |
| Professor > Associate Professor | 4 | 12% |
| Student > Bachelor | 3 | 9% |
| Other | 2 | 6% |
| Other | 3 | 9% |
| Unknown | 10 | 30% |
| Readers by discipline | Count | As % |
|---|---|---|
| Neuroscience | 7 | 21% |
| Medicine and Dentistry | 5 | 15% |
| Biochemistry, Genetics and Molecular Biology | 4 | 12% |
| Agricultural and Biological Sciences | 3 | 9% |
| Immunology and Microbiology | 1 | 3% |
| Other | 1 | 3% |
| Unknown | 12 | 36% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. 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 07 March 2018.
All research outputs
#13,546,001
of 22,961,203 outputs
Outputs from Molecular Neurobiology
#1,704
of 3,477 outputs
Outputs of similar age
#159,528
of 307,967 outputs
Outputs of similar age from Molecular Neurobiology
#32
of 83 outputs
Altmetric has tracked 22,961,203 research outputs across all sources so far. This one is in the 39th percentile – i.e., 39% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,477 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.2. This one is in the 49th percentile – i.e., 49% of its peers scored the same or lower than it.
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We're also able to compare this research output to 83 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 61% of its contemporaries.