| Title |
Vascular deficiency of Smad4 causes arteriovenous malformations: a mouse model of Hereditary Hemorrhagic Telangiectasia
|
|---|---|
| Published in |
Angiogenesis, February 2018
|
| DOI | 10.1007/s10456-018-9602-0 |
| Pubmed ID | |
| Authors |
Angela M. Crist, Amanda R. Lee, Nehal R. Patel, Dawn E. Westhoff, Stryder M. Meadows |
| Abstract |
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder that leads to abnormal connections between arteries and veins termed arteriovenous malformations (AVM). Mutations in TGFβ pathway members ALK1, ENG and SMAD4 lead to HHT. However, a Smad4 mouse model of HHT does not currently exist. We aimed to create and characterize a Smad4 endothelial cell (EC)-specific, inducible knockout mouse (Smad4f/f;Cdh5-CreERT2) that could be used to study AVM development in HHT. We found that postnatal ablation of Smad4 caused various vascular defects, including the formation of distinct AVMs in the neonate retina. Our analyses demonstrated that increased EC proliferation and size, altered mural cell coverage and distorted artery-vein gene expression are associated with Smad4 deficiency in the vasculature. Furthermore, we show that depletion of Smad4 leads to decreased Vegfr2 expression, and concurrent loss of endothelial Smad4 and Vegfr2 in vivo leads to AVM enlargement. Our work provides a new model in which to study HHT-associated phenotypes and links the TGFβ and VEGF signaling pathways in AVM pathogenesis. |
X Demographics
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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 56 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 56 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 10 | 18% |
| Student > Ph. D. Student | 8 | 14% |
| Other | 4 | 7% |
| Student > Bachelor | 4 | 7% |
| Student > Master | 4 | 7% |
| Other | 8 | 14% |
| Unknown | 18 | 32% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 13 | 23% |
| Biochemistry, Genetics and Molecular Biology | 13 | 23% |
| Agricultural and Biological Sciences | 4 | 7% |
| Neuroscience | 2 | 4% |
| Design | 2 | 4% |
| Other | 5 | 9% |
| Unknown | 17 | 30% |
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 24 February 2018.
All research outputs
#18,589,103
of 23,025,074 outputs
Outputs from Angiogenesis
#401
of 538 outputs
Outputs of similar age
#256,887
of 330,824 outputs
Outputs of similar age from Angiogenesis
#12
of 17 outputs
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