Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2003-6-16
pubmed:abstractText
During the early stage of angiogenesis, neovascular sprouts are composed primarily of endothelial cells. As they mature, microvessels acquire a coating of mural cells, which are critical for the development and maintenance of a functional vasculature. Though growth factor regulation of mural cell recruitment has been extensively investigated, the intracellular signaling events involved in this process remain poorly understood. Among the intracellular kinases implicated in angiogenesis, the p38 MAPK has been shown to transduce signals critical for vascular remodeling and maturation. The rat aorta model of angiogenesis was used to further investigate the role of this signaling pathway in the recruitment of mural cells during angiogenesis. The p38 MAPK inhibitor SB203580 selectively blocked mural cell recruitment, resulting in the formation of naked endothelial tubes without mural cells. SB203580 inhibited angiopoietin-1-induced mural cell recruitment without influencing angiopoietin-1-stimulated endothelial sprouting. Adenoviral vector-mediated expression of a dominant negative form of p38 MAPK significantly reduced mural cell recruitment, whereas overexpression of a constitutively activated form of MKK6, an upstream activator of p38 MAPK, increased mural cell number. These results indicate that the p38 MAPK signaling pathway plays a critical role in mural cell recruitment during neovascularization and may represent a therapeutic target in angiogenesis-related disorders.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1018-1172
pubmed:author
pubmed:copyrightInfo
Copyright 2003 S. Karger AG, Basel
pubmed:issnType
Print
pubmed:volume
40
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
140-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12808350-Adenoviridae, pubmed-meshheading:12808350-Angiotensin I, pubmed-meshheading:12808350-Animals, pubmed-meshheading:12808350-Aorta, pubmed-meshheading:12808350-Calcium-Calmodulin-Dependent Protein Kinases, pubmed-meshheading:12808350-Cell Movement, pubmed-meshheading:12808350-Cells, Cultured, pubmed-meshheading:12808350-Endothelium, Vascular, pubmed-meshheading:12808350-Enzyme Inhibitors, pubmed-meshheading:12808350-Genetic Vectors, pubmed-meshheading:12808350-Imidazoles, pubmed-meshheading:12808350-MAP Kinase Kinase 6, pubmed-meshheading:12808350-Male, pubmed-meshheading:12808350-Microscopy, Electron, pubmed-meshheading:12808350-Mitogen-Activated Protein Kinases, pubmed-meshheading:12808350-Models, Animal, pubmed-meshheading:12808350-Neovascularization, Physiologic, pubmed-meshheading:12808350-Pericytes, pubmed-meshheading:12808350-Pyridines, pubmed-meshheading:12808350-Rats, pubmed-meshheading:12808350-Rats, Inbred F344, pubmed-meshheading:12808350-p38 Mitogen-Activated Protein Kinases
pubmed:articleTitle
Requisite role of p38 MAPK in mural cell recruitment during angiogenesis in the rat aorta model.
pubmed:affiliation
Department of Pathology, University of Washington, Seattle, WA, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.