en
Scientific article
English

Generation of human inflammation-resistant endothelial progenitor cells by A20 gene transfer

Published inJournal of vascular research, vol. 47, no. 2, p. 157-167
Publication date2010
Abstract

Inflammatory activation of the vascular endothelium is a major contributory factor to ischemic cardiovascular disease. Endothelial progenitor cells (EPCs) are being investigated for the treatment of ischemic disease or to coat vein grafts for bypass surgery. As an inflammatory environment might reduce their therapeutic efficacy, we sought to generate EPCs that are less sensitive to inflammatory activation. EPCs were obtained from human umbilical cord blood and transduced with a lentiviral vector for stable expression of A20, an anti-inflammatory protein. Nontransduced and green-fluorescent-protein-transduced cells were used as controls. Expression of A20 by EPCs did not modify cell morphology or expression of a panel of 20 proteins known to contribute to angiogenesis. Also, A20 had no effect on the capacity of EPCs to form tube-like structures in Matrigel. A20 expression reduced EPC activation by tumor necrosis factor-alpha and interleukin-1beta as determined from changes in vascular cell adhesion molecule 1 and E-selectin expression and decreased monocyte transmigration through a monolayer of EPCs. In conclusion, EPCs can be genetically modified to overexpress A20 in a stable fashion. These cells become less sensitive to inflammatory stimuli. This may be of interest in cell-based therapeutic approaches for clinical settings where inflammation is an important pathogenic factor.

Keywords
  • Angiogenic Proteins/genetics
  • Cells, Cultured
  • Culture Media, Conditioned/metabolism
  • E-Selectin/genetics/metabolism
  • Endothelial Cells/*immunology
  • Fetal Blood/cytology/immunology
  • Fetal Stem Cells/*immunology
  • Gene Expression Regulation
  • Genetic Vectors
  • Humans
  • Inflammation/genetics/immunology/*prevention & control
  • Inflammation Mediators/metabolism
  • Interleukin-1beta/metabolism
  • Intracellular Signaling Peptides and Proteins/genetics
  • Lentivirus/genetics
  • Leukocyte Rolling
  • Monocytes/immunology
  • Neovascularization, Physiologic/genetics
  • Nuclear Proteins/*biosynthesis/genetics
  • RNA, Messenger/metabolism
  • *Transduction, Genetic
  • Tumor Necrosis Factor-alpha/metabolism
  • Vascular Cell Adhesion Molecule-1/genetics/metabolism
Citation (ISO format)
LIU, Jia Wei et al. Generation of human inflammation-resistant endothelial progenitor cells by A20 gene transfer. In: Journal of vascular research, 2010, vol. 47, n° 2, p. 157–167. doi: 10.1159/000250094
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ISSN of the journal1018-1172
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