This Article Full Text Full Text (PDF) Other Versions of this Article: MCB.00443-07v1 28/2/794    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lei, L. Articles by Giordano, F. J. Search for Related Content PubMed PubMed Citation Articles by Lei, L. Articles by Giordano, F. J.

Endothelial Expression of β1 Integrin Is Required for Embryonic Vascular Patterning and Postnatal Vascular Remodeling

Li Lei,^1, Dinggang Liu,^1, Yan Huang,¹ Ion Jovin,¹ Shaw-Yung Shai,² Themis Kyriakides,³ Robert S. Ross,^4* and Frank J. Giordano^1*

Yale University School of Medicine, Section of Cardiovascular Medicine, New Haven, Connecticut 06510,¹ Tulane University School of Medicine, New Orleans, Louisiana,² Yale University, Department of Pathology, New Haven, Connecticut 06510,³ University of California San Diego and San Diego VA Healthcare, Department of Medicine, Cardiology Division, San Diego, California 92161⁴

Received 14 March 2007/ Returned for modification 12 April 2007/ Accepted 4 October 2007

The largest subgroup of integrins is that containing the β1 subunit. β1 integrins have been implicated in a wide array of biological processes ranging from adhesion to cell growth, organogenesis, and mechanotransduction. Global deletion of β1 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 β1 integrin in the vasculature, we conditionally deleted the β1 gene in the endothelium. Homozygous deletion of β1 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 β1 gene deletion did not diminish fetal or postnatal survival, but it reduced β1 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 β1 integrin is required for developmental vascular patterning and that endothelial β1 gene dosing has significant functional effects on vascular remodeling in the adult. Understanding how β1 integrin expression is modulated may have significant clinical importance.

Published ahead of print on 5 November 2007.

L.L. and D.L. contributed equally to this study.

This article has been cited by other articles:

• Carlson, T. R., Hu, H., Braren, R., Kim, Y. H., Wang, R. A. (2008). Cell-autonomous requirement for {beta}1 integrin in endothelial cell adhesion, migration and survival during angiogenesis in mice. Development 135: 2193-2202 [Abstract] [Full Text]  
• Hao, Z., Huang, Y., Cleman, J., Jovin, I. S., Vale, W. W., Bale, T. L., Giordano, F. J. (2008). Urocortin2 inhibits tumor growth via effects on vascularization and cell proliferation. Proc. Natl. Acad. Sci. USA 105: 3939-3944 [Abstract] [Full Text]