Endothelial expression of β1 integrin is required for embryonic vascular patterning and postnatal vascular remodeling

The largest subgroup of integrins is that containing the beta 1 subunit. beta 1 integrins have been implicated in a wide array of biological processes ranging from adhesion to cell growth, organogenesis, and mechanotransduction. Global deletion of beta 1 integrin expression results in embryonic death at ca. embryonic day 5 (E5), a developmental time point too early to determine the effects of this integrin on vascular development. To elucidate the specific role of beta 1 integrin in the vasculature, we conditionally deleted the beta 1 gene in the endothelium. Homozygous deletion of beta 1 integrins in the endothelium resulted in failure of normal vascular patterning, severe fetal growth retardation, and embryonic death at E9.5 to 10, although there were no overt effects on vasculogenesis. Heterozygous endothelial beta 1 gene deletion did not diminish fetal or postnatal survival, but it reduced beta 1 subunit expression in endothelial cells from adult mice by approximately 40%. These mice demonstrated abnormal vascular remodeling in response to experimentally altered in vivo blood flow and diminished vascularization in healing wounds. These data demonstrate that endothelial expression of beta 1 integrin is required for developmental vascular patterning and that endothelial beta 1 gene dosing has significant functional effects on vascular remodeling in the adult. Understanding how beta 1 integrin expression is modulated may have significant clinical importance.