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J Biol Chem. 2004 Feb 13;279(7):6143-51. Epub 2003 Nov 18.

Enhanced in vitro proliferation of aortic endothelial cells from plasminogen activator inhibitor-1-deficient mice.

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  • 1W. M. Keck Center for Transgene Research and the Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, USA. vploplis@nd.edu

Abstract

A number of studies have identified a role for plasminogen activator inhibitor-1 (PAI-1) in regulating angiogenesis, although results from these investigations have been controversial. Among key cellular components of an angiogenic vessel are endothelial cells (ECs), which are known to express several components of the fibrinolytic system, including PAI-1. Thus, alterations in expression of this protein may have direct effects on cell functions involved in vascular development. In this study, ECs were isolated from sections of murine arterial trees from wild-type and PAI-1-deficient mice, and low passage (passages 3-4) homogeneous subpopulations of these cells were obtained by immunomagnetic absorption to antibodies against CD105/CD106. The homogeneity of these cells was further assessed by immunohistochemistry and quantitative real-time reverse transcription-PCR analysis of a number of EC markers. Comparative analyses of EC proliferation (one event associated with angiogenesis) in wild-type and PAI-1-deficient ECs demonstrated enhanced rates of cell growth for PAI-1-deficient cells relative to wild-type cells. Additional studies demonstrated similar levels of both vascular endothelial growth factor (VEGF) mRNA and protein and enhanced levels of VEGF receptor-1 (Flt-1) mRNA in PAI-1-deficient cells relative to wild-type cells. Immunohistochemical analyses indicated that phosphorylation of Akt was also enhanced in PAI-1-deficient cells, implicating VEGF-induced cell signaling alterations in PAI-1-deficient cells, the result of which may contribute to alterations in cell proliferation.

PMID:
14625301
[PubMed - indexed for MEDLINE]
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