title: Heme oxygenase-1 protects endothelial cells from the toxicity of air pollutant chemicals.
abstract: Diesel exhaust particles (DEPs) are a major component of diesel emissions, responsible for a large portion of their toxicity. In this study, we examined the toxic effects of DEPs on endothelial cells and the role of DEP-induced heme oxygenase-1 (HO-1) expression. Human microvascular endothelial cells (HMECs) were treated with an organic extract of DEPs from an automobile engine (A-DEP) or a forklift engine (F-DEP) for 1 and 4h. ROS generation, cell viability, lactate dehydrogenase leakage, expression of HO-1, inflammatory genes, cell adhesion molecules and unfolded protein respone (UPR) gene were assessed. HO-1 expression and/or activity were inhibited by siRNA or tin protoporphyrin (Sn PPIX) and enhanced by an expression plasmid or cobalt protoporphyrin (CoPPIX). Exposure to 25μg/ml of A-DEP and F-DEP significantly induced ROS production, cellular toxicity and greater levels of inflammatory and cellular adhesion molecules but to a different degree. Inhibition of HO-1 enzymatic activity with SnPPIX and silencing of the HO-1 gene by siRNA enhanced DEP-induced ROS production, further decreased cell viability and increased expression of inflammatory and cell adhesion molecules. On the other hand, overexpression of the HO-1 gene by a pcDNA 3.1D/V5-HO-1 plasmid significantly mitigated ROS production, increased cell survival and decreased the expression of inflammatory genes. HO-1 expression protected HMECs from DEP-induced prooxidative and proinflammatory effects. Modulation of HO-1 expression could potentially serve as a therapeutic target in an attempt to inhibit the cardiovascular effects of ambient PM.
authors.affiliation: Division of Cardiology, David Geffen School of Medicine, University of California-Los Angeles, 10833 Le Conte Avenue, CHS 43-264, Los Angeles, CA 90095.
authors.forename: Akeem
authors.initials: A
authors.lastname: Lawal
authors.affiliation: Division of Cardiology, David Geffen School of Medicine, University of California-Los Angeles, 10833 Le Conte Avenue, CHS 43-264, Los Angeles, CA 90095.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Division of Cardiology, David Geffen School of Medicine, University of California-Los Angeles, 10833 Le Conte Avenue, CHS 43-264, Los Angeles, CA 90095.
authors.forename: Michael
authors.initials: M
authors.lastname: Dittmar
authors.affiliation: Division of Cardiology, David Geffen School of Medicine, University of California-Los Angeles, 10833 Le Conte Avenue, CHS 43-264, Los Angeles, CA 90095.
authors.forename: Aaron
authors.initials: A
authors.lastname: Lulla
authors.affiliation: Division of Cardiology, David Geffen School of Medicine, University of California-Los Angeles, 10833 Le Conte Avenue, CHS 43-264, Los Angeles, CA 90095.
authors.forename: Jesus A
authors.initials: JA
authors.lastname: Araujo
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D004791:Enzyme Inhibitors / Q000633:toxicity; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D052638:Particulate Matter / Q000633:toxicity*; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D018570:Risk Assessment; D013997:Time Factors; D014162:Transfection; D056811:Unfolded Protein Response / Q000187:drug effects; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D015815:Cell Adhesion Molecules; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D052638:Particulate Matter; D017382:Reactive Oxygen Species; D001335:Vehicle Emissions; D007770:L-Lactate Dehydrogenase; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1
keywords: Air pollution; Diesel exhaust particles; Endothelial cells; Heme oxygenase-1; Inflammation; Reactive oxygen species