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Endothelial Expression of Beta‐1 Integrin Is Required for Embryonic Vascular Patterning and Postnatal Vascular Remodeling
Author(s) -
lei li,
Liu Dinggang,
Huang Yan,
Jovin Ion,
Shai ShawYung,
Kyriakides Themis,
Ross Robert,
Giordano Frank
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1122.11
Subject(s) - vasculogenesis , integrin , biology , embryonic stem cell , microbiology and biotechnology , endothelium , angiogenesis , vascular endothelial growth factor a , vascular endothelial growth factor , endocrinology , gene , cancer research , stem cell , genetics , cell , vegf receptors , progenitor cell
The largest subgroup of integrins is that containing the β1 subunit. Global deletion of β1 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 β1 integrin in the vasculature, we conditionally deleted the β1 gene in the endothelium using Cre/LoxP techniques. Homozygous deletion of β1 integrins in the endothelium resulted in failure of normal vascular patterning, severe fetal growth retardation, and embryonic death at E9.5‐10, although there were no overt effects on vasculogenesis (Fig. 1). Heterozygous endothelial β1 gene deletion did not diminish fetal or postnatal survival, but reduced β1 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 (Fig. 2). 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.