Journal
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Volume 33, Issue 5, Pages 943-U180Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.112.300566
Keywords
cell adhesion molecule; endothelial cell; extracellular matrix; hypoxia; vascular remodeling
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Funding
- National Multiple Sclerosis Society
- Harry Weaver Neuroscience Scholar Award [JF 2125A1/1]
- National Institutes of Health RO1 grant [NS060770]
- [FG 1879-A-1]
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Objective-Laminin is a major component of the vascular basal lamina, implying that laminin receptors, such as alpha 6 beta 1 and alpha 6 beta 4 integrins, may regulate vascular remodeling and homeostasis. Previous studies in the central nervous system have shown that beta 4 integrin is expressed by only a fraction of cerebral vessels, but defining the vessel type and cellular source of beta 4 integrin has proved controversial. The goal of this study was to define the class of vessel and cell type expressing beta 4 integrin in cerebral vessels and to examine its potential role in vascular remodeling. Approach and Results-Dual-immunofluorescence showed that beta 4 integrin is expressed predominantly in arterioles, both in the central nervous system and in peripheral organs. Cell-specific knockouts of beta 4 integrin revealed that beta 4 integrin expression in cerebral vessels is derived from endothelial cells, not astrocytes or smooth muscle cells. Lack of endothelial beta 4 integrin had no effect on vascular development, integrity, or endothelial proliferation, but in the hypoxic central nervous system, its absence led to defective arteriolar remodeling and associated transforming growth factor-beta signaling. Conclusions-These results define high levels of beta 4 integrin in arteriolar endothelial cells and demonstrate a novel link among beta 4 integrin, transforming growth factor-beta signaling, and arteriolar remodeling in cerebral vessels. (Arterioscler Thromb Vasc Biol. 2013; 33: 943-953.)
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