title: Endothelial expression of beta1 integrin is required for embryonic vascular patterning and postnatal vascular remodeling.
abstract: The largest subgroup of integrins is that containing the beta1 subunit. beta1 integrins have been implicated in a wide array of biological processes ranging from adhesion to cell growth, organogenesis, and mechanotransduction. Global deletion of beta1 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 beta1 integrin in the vasculature, we conditionally deleted the beta1 gene in the endothelium. Homozygous deletion of beta1 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 beta1 gene deletion did not diminish fetal or postnatal survival, but it reduced beta1 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 beta1 integrin is required for developmental vascular patterning and that endothelial beta1 gene dosing has significant functional effects on vascular remodeling in the adult. Understanding how beta1 integrin expression is modulated may have significant clinical importance.
authors.affiliation: BCMM 436C, 295 Congress Ave., New Haven, CT 06510, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Lei
authors.forename: Dinggang
authors.initials: D
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Ion
authors.initials: I
authors.lastname: Jovin
authors.forename: Shaw-Yung
authors.initials: SY
authors.lastname: Shai
authors.forename: Themis
authors.initials: T
authors.lastname: Kyriakides
authors.forename: Robert S
authors.initials: RS
authors.lastname: Ross
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Giordano
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D020964:Embryo Loss / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian / Q000098:blood supply* / Q000196:embryology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D006720:Homozygote; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014945:Wound Healing
chemical_list: D019012:Integrin beta1