Vascular Endothelial Growth Factor Induces Expression of the Antiapoptotic Proteins Bcl-2 and A1 in Vascular Endothelial Cells*
- From the Departments of Cardiovascular Research and‡Molecular Oncology, Genentech, Inc., South San Francisco, California 94080
Abstract
We examined the role of vascular endothelial growth factor (VEGF) in preventing apoptosis in primary human umbilical vein endothelial (HUVE) cells. VEGF was capable of preventing serum starvation-induced apoptosis at concentrations between 10 and 100 ng/ml. The addition of VEGF to serum-starved HUVE cells led to a 5.2-fold induction of Bcl-2 after 36 h and to a transient, 2.4-fold induction of A1 after a 7-h incubation, as quantitated by real time reverse transcriptase-polymerase chain reaction analysis. Western blot analysis demonstrated a 2–3-fold induction of Bcl-2 protein after 18–36 h of exposure to VEGF and a transient induction of A1 after 7 h of VEGF stimulation. Moreover, overexpression of Bcl-2 by means of transient biolistic transfection experiments of HUVE cells was sufficient to prevent endothelial cells from apoptotic cell death in the absence of VEGF. These findings indicate that Bcl-2 plays an important role in mediating the survival activity of VEGF on endothelial cells.
Footnotes
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↵* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵§ To whom correspondence should be addressed: Dept. of Cardiovascular Research, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080. Tel.: 650-225-2968; Fax: 650-225-6327.
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↵1 The abbreviations used are: HUVE cells, human umbilical vein endothelial cells; VEGF, vascular endothelial growth factor; RT-PCR, reverse transcriptase-polymerase chain reaction; GFP, green fluorescent protein.
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↵2 H. P. Gerber, A. McMurtrey, H. Nguyen, Y. Minhong, V. Dixit, and N. Ferrara, submitted for publication.
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- Received March 20, 1998.
- The American Society for Biochemistry and Molecular Biology, Inc.
