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Mol. Cell. Biol. doi:10.1128/MCB.00443-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Endothelial expression of beta-1 integrin is required for embryonic vascular patterning and postnatal vascular remodeling

Yale University School of Medicine, Section of Cardiovascular Medicine, New Haven, CT, 06510; Tulane University School of Medicine, New Orleans, LA, Yale University; Dept. of Pathology, University of California San Diego and San Diego VA Healthcare, Dept. of Medicine, Cardiology Division, San Diego, CA

^* To whom correspondence should be addressed. Email: rross{at}ucsd.edu. frank.giordano{at}yale.edu.

	Abstract

The largest subgroup of integrins is that containing the 1 subunit. 1 integrins have been implicated in a wide array of biological processes ranging from adhesion to cell growth, organogenesis and mechanotransduction. Global deletion of 1 integrin expression results in embryonic lethality at E5, a developmental time point too early to determine the effects of this integrin on vascular development. To elucidate the specific role of 1 integrin in the vasculature, we conditionally deleted the 1 gene in the endothelium. Homozygous deletion of 1 integrins in the endothelium resulted in failure of normal vascular patterning, severe fetal growth retardation, and embryonic death at E9.5-10, although there were no overt effects on vasculogenesis. Heterozygous endothelial 1 gene deletion did not diminish fetal or postnatal survival, but reduced 1 subunit expression in endothelial cells from adult mice 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 1 integrin is required for developmental vascular patterning, and that endothelial 1 gene dosing has significant functional effects on vascular remodeling in the adult. Understanding how 1 integrin expression is modulated may have significant clinical importance.

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