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Endothelium
Journal of Endothelial Cell Research
Volume 15, 2008 - Issue 1-2
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Regular Articles

Antiapoptotic Activities of Bcl-2 Correlate with Vascular Maturation and Transcriptional Modulation of Human Endothelial Cells

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Pages 59-71 | Received 25 Oct 2008, Accepted 28 Mar 2008, Published online: 13 Jul 2009
 

Abstract

Overexpression of a caspase-resistant form of Bcl-2 (D34A) in human umbilical vein endothelial cells (ECs) implanted into immunodeficient mice promotes the maturation of human EC-lined microvessels invested by vascular smooth muscle cells (VSMCs) of mouse origin. In contrast, EC implants not overexpressing Bcl-2 form only simple, uncoated EC tubes. Here the authors compare the phenotypes of vessels formed in vivo and the transcriptomes in vitro of EC expressing different forms of Bcl-2. Wild-type Bcl-2, like the caspase-resistant D34A Bcl-2 mutant, is antiapoptotic in vitro and promotes VSMC recruitment in vivo, whereas a G145E mutant that has diminished antiapoptotic activity in vitro does not promote vessel maturation in vivo. The D34A and wild-type forms of Bcl-2, but not the G145E mutant form of Bcl-2, significantly regulate RNA transcripts previously associated with EC-VSMC interactions and VSMC biology, including matrix Gla protein, insulin-like growth factor–binding protein (IGFBP)-2, matrix metalloproteinase (MMP)-14, ADAM17, stanniocalcin-1, and targets of the nuclear factor (NF)-κ B, cAMP response element-binding (CREB), and activator protein 1 (AP1) transcription factor families. These effects of Bcl-2 on the transcriptome are detected in ECs cultured as angiogenic three-dimensional (3-D) tubes but are attenuated in ECs cultured as 2-D monolayers. Bcl-2–regulated transcription in ECs may contribute to vascular maturation, and support design of tissue engineering strategies using EC.

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