| Title |
β-adrenergic receptor antagonists inhibit vasculogenesis of embryonic stem cells by downregulation of nitric oxide generation and interference with VEGF signalling
|
|---|---|
| Published in |
Cell and Tissue Research, August 2014
|
| DOI | 10.1007/s00441-014-1976-8 |
| Pubmed ID | |
| Authors |
Fatemeh Sharifpanah, Fatjon Saliu, Mohamed M. Bekhite, Maria Wartenberg, Heinrich Sauer |
| Abstract |
The β-adrenoceptor antagonist Propranolol has been successfully used to treat infantile hemangioma. However, its mechanism of action is so far unknown. The hypothesis of this research was that β-adrenoceptor antagonists may interfere with endothelial cell differentiation of stem cells. Specifically, the effects of the non-specific β-adrenergic receptor (β-adrenoceptor) antagonist Propranolol, the β1-adrenoceptor-specific antagonist Atenolol and the β2-adrenoceptor-specific antagonist ICI118,551 on vasculogenesis of mouse embryonic stem (ES) cells were investigated. All three β-blockers dose-dependently downregulated formation of capillary structures in ES cell-derived embryoid bodies and decreased the expression of the vascular cell markers CD31 and VE-cadherin. Furthermore, β-blockers downregulated the expression of fibroblast growth factor-2 (FGF-2), hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor 165 (VEGF165), VEGF receptor 2 (VEGF-R2) and phospho VEGF-R2, as well as neuropilin 1 (NRP1) and plexin-B1 which are essential modulators of embryonic angiogenesis with additional roles in vessel remodelling and arteriogenesis. Under conditions of β-adrenoceptor inhibition, the endogenous generation of nitric oxide (NO) as well as the phosphorylation of endothelial nitric oxide synthase (eNOS) was decreased in embryoid bodies, whereas an increase in NO generation was observed with the NO donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP). Consequently, vasculogenesis of ES cells was restored upon treatment of differentiating ES cells with β-adrenoceptor antagonists in the presence of NO donor. In summary, our data suggest that β-blockers impair vasculogenesis of ES cells by interfering with NO generation which could be the explanation for their anti-angiogenic effects in infantile hemangioma. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 39 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 39 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 7 | 18% |
| Student > Bachelor | 6 | 15% |
| Researcher | 6 | 15% |
| Other | 4 | 10% |
| Student > Master | 3 | 8% |
| Other | 8 | 21% |
| Unknown | 5 | 13% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 11 | 28% |
| Agricultural and Biological Sciences | 7 | 18% |
| Biochemistry, Genetics and Molecular Biology | 4 | 10% |
| Engineering | 4 | 10% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 3% |
| Other | 4 | 10% |
| Unknown | 8 | 21% |
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 19 August 2014.
All research outputs
#19,236,357
of 23,839,820 outputs
Outputs from Cell and Tissue Research
#1,706
of 2,279 outputs
Outputs of similar age
#170,753
of 237,669 outputs
Outputs of similar age from Cell and Tissue Research
#18
of 26 outputs
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