| Pro-inflammatory angiogenesis is mediated by p38 MAP kinase. | |
| | |
MedLine Citation:
|
PMID: 20803566 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Chronic inflammation is tightly linked to diseases associated with endothelial dysfunction including aberrant angiogenesis. To better understand the endothelial role in pro-inflammatory angiogenesis, we analyzed signaling pathways in continuously activated endothelial cells, which were either chronically exposed to soluble TNF or the reactive oxygen species (ROS) generating H2O2, or express active transmembrane TNF. Testing in an in vitro capillary sprout formation assay, continuous endothelial activation increased angiogenesis dependent on activation of p38 MAP kinase, NADPH oxidase, and matrix metalloproteinases (MMP). p38 MAP kinase- and MMP-9-dependent angiogenesis in our assay system may be part of a positive feed forward autocrine loop because continuously activated endothelial cells displayed up-regulated ROS production and subsequent endothelial TNF expression. The pro-angiogenic role of the p38 MAP kinase in continuously activated endothelial cells was in stark contrast to the anti-angiogenic activity of the p38 MAP kinase in unstimulated control endothelial cells. In vivo, using an experimental prostate tumor, pharmacological inhibition of p38 MAP kinase demonstrated a significant reduction in tumor growth and in vessel density, suggesting a pro-angiogenic role of the p38 MAP kinase in pathological angiogenesis in vivo. In conclusion, our results suggest that continuous activation of endothelial cells can cause a switch of the p38 MAP kinase from anti-angiogenic to pro-angiogenic activities in conditions which link oxidative stress and autocrine TNF production. |
| | |
Authors:
|
Gangaraju Rajashekhar; Malgorzata Kamocka; Abby Marin; Mark A Suckow; William R Wolter; Sunil Badve; Aravind Raj Sanjeevaiah; Kevin Pumiglia; Elliot Rosen; Matthias Clauss |
Related Documents
:
|
16965246 - Diallyl trisulfide inhibits angiogenic features of human umbilical vein endothelial cel... 12189156 - Subcellular targeting and agonist-induced site-specific phosphorylation of endothelial ... 20416296 - Involvement of androgen receptor in nitric oxide production induced by icariin in human... 11053436 - Inhibition of angiogenesis by a mouse sprouty protein. 8650176 - Receptor stimulation causes slow inhibition of irk1 inwardly rectifying k+ channels by ... 9876236 - The immune-endocrine loop during aging: role of growth hormone and insulin-like growth ... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Journal of cellular physiology Volume: 226 ISSN: 1097-4652 ISO Abbreviation: J. Cell. Physiol. Publication Date: 2011 Mar |
Date Detail:
|
Created Date: 2010-12-30 Completed Date: 2011-01-27 Revised Date: 2011-09-22 |
Medline Journal Info:
|
Nlm Unique ID: 0050222 Medline TA: J Cell Physiol Country: United States |
Other Details:
|
Languages: eng Pagination: 800-8 Citation Subset: IM |
Copyright Information:
|
Copyright © 2010 Wiley-Liss, Inc. |
Affiliation:
|
Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. rgangara@iupui.edu |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Cell Proliferation / drug effects Endothelial Cells / drug effects, enzymology, pathology Enzyme Activation / drug effects Humans Hydrogen Peroxide / pharmacology Inflammation / complications*, enzymology*, pathology MAP Kinase Signaling System / drug effects Matrix Metalloproteinase 9 / metabolism Mice Models, Biological Neoplasms / blood supply, enzymology, pathology Neovascularization, Pathologic / complications*, enzymology* Rats Solubility / drug effects Tumor Necrosis Factor-alpha / metabolism, pharmacology p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
|
R01 CA081419-09/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Tumor Necrosis Factor-alpha; 7722-84-1/Hydrogen Peroxide; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 3.4.24.35/Matrix Metalloproteinase 9 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Comparative lipidomic profiling of xylose-metabolizing S. cerevisiae and its parental strain in diff...
Next Document: The styloid process and its relationship to the facial and hypoglossal nerves.