Endothelial beta 4 Integrin Is Predominantly Expressed in Arterioles, Where It Promotes Vascular Remodeling in the Hypoxic Brain

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.)