E1-E4+ adenoviral gene transfer vectors function as a 'pro-life' signal to promote survival of primary human endothelial cells

Ramachandran Ramalingam, Shahin Rafii, Stefan Worgall, Douglas E. Brough, Ronald Crystal

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Although endothelial cells are quiescent and long-lived in vivo, when they are removed from blood vessels and cultured in vitro they die within days to weeks. In studies of the interaction of E1-E4+ replication-deficient adenovirus (Ad) vectors and human endothelium, the cells remained quiescent and were viable for prolonged periods. Evaluation of these cultures showed that E1-E4+ Ad vectors provide an 'antiapoptotic' signal that, in association with an increase in the ratio of Bcl2 to Bax levels, induces the endothelial cells to enter a state of 'suspended animation,' remaining viable for at least 30 days, even in the absence of serum and growth factors. Although the mechanisms initiating these events are unclear, the antiapoptoic signal requires the presence of E4 genes in the vector genome, suggesting that one or more E4 open reading frames of subgroup C Ad initiate a 'pro- life' program that modifies cultured endothelial cells to survive for prolonged periods.

Original languageEnglish
Pages (from-to)2936-2944
Number of pages9
JournalBlood
Volume93
Issue number9
Publication statusPublished - 1 May 1999
Externally publishedYes

Fingerprint

Gene transfer
Endothelial cells
Endothelial Cells
Adenoviridae
Genes
Human Adenoviruses
Blood vessels
Animation
Open Reading Frames
Endothelium
Blood Vessels
Cultured Cells
Intercellular Signaling Peptides and Proteins
Genome
Serum

ASJC Scopus subject areas

  • Immunology
  • Biochemistry
  • Hematology
  • Cell Biology

Cite this

E1-E4+ adenoviral gene transfer vectors function as a 'pro-life' signal to promote survival of primary human endothelial cells. / Ramalingam, Ramachandran; Rafii, Shahin; Worgall, Stefan; Brough, Douglas E.; Crystal, Ronald.

In: Blood, Vol. 93, No. 9, 01.05.1999, p. 2936-2944.

Research output: Contribution to journalArticle

Ramalingam, Ramachandran ; Rafii, Shahin ; Worgall, Stefan ; Brough, Douglas E. ; Crystal, Ronald. / E1-E4+ adenoviral gene transfer vectors function as a 'pro-life' signal to promote survival of primary human endothelial cells. In: Blood. 1999 ; Vol. 93, No. 9. pp. 2936-2944.
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