Rac-dependent monocyte chemoattractant protein-1 production is induced by nutrient deprivation

Neuza H.M. Lopes, Sanjay S. Vasudevan, David Gregg, Balakrishnan Selvakumar, Patrick J. Pagano, Herve Kovacic, Pascal J. Goldschmidt-Clermont

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Under ischemic conditions, the vessel wall recruits inflammatory cells. Human aortic endothelial cells (HAECs) exposed to hypoxia followed by reoxygenation produce monocyte chemoattractant protein-1 (MCP-1); however, most experiments have been performed in the presence of nutrient deprivation (ND). We hypothesized that ND rather than hypoxia mediates endothelial MCP-1 production during ischemia, and that the small GTP-binding protein Rac1 and reactive oxygen species (ROS) are involved in this process. ND was generated by shifting HAECs from 10% to 1% FBS. Superoxide production by HAECs was increased 6 to 24 hours after ND, peaking at 18 hours. MCP-1 production was increased over a similar time frame, but peaked later at 24 hours. These effects were blocked by treatment with antioxidants such as superoxide dismutase mimetic and N-acetylcysteine (NAC), or NADPH oxidase inhibitors, DPI and gp91ds-tat. Superoxide and MCP-1 production were enhanced by RacV12 (constitutively active) in the absence of ND, and were inhibited by RacN17 (dominant-negative) adenoviral transduction under ND, suggesting that the small G-protein Rac1 is required. In conclusion, ND, an important component of ischemia, is sufficient to induce MCP-1 production by HAECs, and such production requires a functional Rac1, redox-dependent pathway.

Original languageEnglish (US)
Pages (from-to)798-805
Number of pages8
JournalCirculation research
Volume91
Issue number9
DOIs
StatePublished - Nov 1 2002

Keywords

  • Ischemia
  • Monocyte chemoattractant protein-1
  • Nutrient deprivation
  • Rac
  • Superoxide

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Lopes, N. H. M., Vasudevan, S. S., Gregg, D., Selvakumar, B., Pagano, P. J., Kovacic, H., & Goldschmidt-Clermont, P. J. (2002). Rac-dependent monocyte chemoattractant protein-1 production is induced by nutrient deprivation. Circulation research, 91(9), 798-805. https://doi.org/10.1161/01.RES.0000040421.54108.81