Unbound MEDLINE

DEP induction of ROS in capillary-like endothelial tubes leads to VEGF-A expression.

Abstract

Inhalation of diesel exhaust particles (DEPs) is associated with pulmonary and cardiovascular disease. One contributor to pathogenesis is inhaled particles reaching and injuring the lung capillary endothelial cells, and possibly gaining access to the blood stream. Using in vitro capillary tubes as a simplified vascular model system for this process, it was previously shown that DEPs induce the redistribution of vascular endothelial cell-cadherin (VE-Cad) away from the plasma membrane to intracellular locations. This allowed DEPs into the cell cytoplasm and tube lumen, suggesting the tubes may have become permeable (Chao et al., 2011). Here some of the mechanisms responsible for endothelial tube changes after DEP exposure were examined. The results demonstrate that endothelial tube cells mounted an oxidative stress response to DEP exposure. Hydrogen peroxide and oxidized proteins were detected after 24h of exposure to DEPs. Particles induced relocalization of Nrf2 from the cytoplasm to the nucleus, upregulating the expression of the enzyme heme oxygenase-1 (HO-1). Surprisingly, vascular endothelial cell growth factor-A (VEGF-A), initially termed "vascular permeability factor" (VPF), was found to be up-regulated in response to the HO-1 expression induced by DEPs. Similar to DEPs, applied VEGF-A induced relocalization of VE-Cadherin from the cell membrane surface to an intracellular location, and relocalization of VE-cadherin was associated with permeability. These data suggest that the DEPs may induce or contribute to the permeability of capillary-like endothelial tube cells via induction of HO-1 and VEGF-A.

Links

  • Publisher Full Text

    • Authors

    Chao MW, Po IP, Laumbach RJ, Koslosky J, Cooper K, Gordon MK

    Institution

    Pharmacology and Toxicology, Rutgers University, Piscataway, NJ 08854, USA.

    Source

    Toxicology 297:1-3 2012 Jul 16 pg 34-46

    MeSH

    Capillaries
    Cell Membrane Permeability
    Cells, Cultured
    Endothelial Cells
    Enzyme Induction
    Gene Expression Regulation
    Heme Oxygenase-1
    Human Umbilical Vein Endothelial Cells
    Humans
    Reactive Oxygen Species
    Vascular Endothelial Growth Factor A
    Vehicle Emissions

    Pub Type(s)

    Comparative Study
    Journal Article
    Research Support, N.I.H., Extramural

    Language

    eng

    PubMed ID

    22507881