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 journalArticlepeer-review

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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