| Notch3 is critical for proper angiogenesis and mural cell investment. | |
| | |
MedLine Citation:
|
PMID: 20689064 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
RATIONALE: The heterotypic interactions of endothelial cells and mural cells (smooth muscle cells or pericytes) are crucial for assembly, maturation, and subsequent function of blood vessels. Yet, the molecular mechanisms underlying their association have not been fully defined. OBJECTIVE: Our previous in vitro studies indicated that Notch3, which is expressed in mural cells, mediates these cell-cell interactions. To assess the significance of Notch3 on blood vessel formation in vivo, we investigated its role in retinal angiogenesis. METHODS AND RESULTS: We show that Notch3-deficient mice exhibit reduced retinal vascularization, with diminished sprouting and vascular branching. Moreover, Notch3 deletion impairs mural cell investment, resulting in progressive loss of vessel coverage. In an oxygen-induced retinopathy model, we demonstrate that Notch3 is induced in hypoxia and interestingly, pathological neovascularization is decreased in retinas of Notch3-null mice. Analysis of oxygen-induced retinopathy mediators revealed that angiopoietin-2 expression is significantly reduced in the absence of Notch3. Furthermore, in vitro experiments showed that Notch3 is sufficient for angiopoietin-2 induction, and this expression is additionally enhanced in the presence of hypoxia-inducible factor 1α. CONCLUSIONS: These results provide compelling evidence that Notch3 is important for the investment of mural cells and is a critical regulator of developmental and pathological blood vessel formation. |
| | |
Authors:
|
Hua Liu; Wenbo Zhang; Simone Kennard; Ruth B Caldwell; Brenda Lilly |
Related Documents
:
|
15173094 - Synergistic effect of histone deacetylase inhibitors fk228 and m-carboxycinnamic acid b... 19845614 - Oxygen sensing in the carotid body. 1175584 - Effect of ethanol on the metabolism of the white blood cells. 8386454 - Mitochondria as a source of reactive oxygen species during reductive stress in rat hepa... 18762964 - Development of the human insular cortex: differentiation, proliferation, cell death, an... 22102824 - Caenorhabditis elegans cyclin d/cdk4 and cyclin e/cdk2 induce distinct cell cycle re-en... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-08-05 |
Journal Detail:
|
Title: Circulation research Volume: 107 ISSN: 1524-4571 ISO Abbreviation: Circ. Res. Publication Date: 2010 Oct |
Date Detail:
|
Created Date: 2010-10-01 Completed Date: 2010-10-22 Revised Date: 2012-05-07 |
Medline Journal Info:
|
Nlm Unique ID: 0047103 Medline TA: Circ Res Country: United States |
Other Details:
|
Languages: eng Pagination: 860-70 Citation Subset: IM |
Affiliation:
|
National Children's Research Institute, The Ohio State University, Columbus, OH 43205, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Angiopoietin-2
/
genetics Animals Anoxia / physiopathology Aorta / cytology, physiology Cell Communication / physiology Cells, Cultured Endothelial Cells / cytology, physiology Gene Expression Regulation / physiology Humans Hypoxia-Inducible Factor 1, alpha Subunit / metabolism Mice Mice, Mutant Strains Muscle, Smooth, Vascular / cytology, physiology* Neovascularization, Pathologic / physiopathology* Neovascularization, Physiologic / physiology* Oxygen / toxicity Pericytes / cytology, physiology* Receptors, Notch / genetics*, metabolism Retinal Vessels / cytology, physiology |
| Grant Support | |
ID/Acronym/Agency:
|
R01 HL076428/HL/NHLBI NIH HHS; R01 HL076428-01A2/HL/NHLBI NIH HHS; R01 HL076428-02/HL/NHLBI NIH HHS; R01 HL076428-03/HL/NHLBI NIH HHS; R01 HL076428-04/HL/NHLBI NIH HHS; R01 HL076428-05/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Angiopoietin-2; 0/HIF1A protein, human; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/NOTCH3 protein, human; 0/Notch3 protein, mouse; 0/Receptors, Notch; 7782-44-7/Oxygen |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Receptor-independent cardiac protein kinase Calpha activation by calpain-mediated truncation of regu...
Next Document: Cardiac small conductance Ca2+-activated K+ channel subunits form heteromultimers via the coiled-coi...