title: Mechanisms underlying nano-sized air-pollution-mediated progression of atherosclerosis: carbon black causes cytotoxic injury/inflammation and inhibits cell growth in vascular endothelial cells.
abstract: BACKGROUND
  Epidemiological studies indicate a significant link between exposure to environmental air pollution and mortality and morbidity from ischemic heart disease. Because nanoparticles can translocate into blood circulation, the present study aimed to clarify their direct effects on human vascular endothelial cells (ECs).
  
  
  RESULTS
  Human umbilical vein ECs (HUVECs) were treated with carbon black (CB), a component of diesel exhaust particles, for 24 h. CB induced cytotoxic morphological changes such as cytosolic vacuole formation, cell disorientation and decreased density. Lactate dehydrogenase assay revealed that CB induced cytotoxic injury in both the cells and plasma membranes. Proliferation assay showed that CB inhibited cell growth. Monocyte chemoattractant protein-1 but not vascular cell adhesion molecule-1 was induced by CB. CB reduced the expressions of connexin37 and endothelial nitric oxide (NO) synthase. Microarray analysis revealed the induction of pro-inflammatory molecules by CB.
  
  
  CONCLUSIONS
  The present results demonstrate for the first time that CB directly affects the endothelium, causing cytotoxic injury, inflammatory responses, and inhibition of cell growth. As EC injury/inflammation and membrane disintegration are related to the initiation of atherosclerosis, and NO is anti-atherogenic and anti-thrombogenic, the direct effects of nanoparticles on ECs may represent one mechanism behind environmental air pollution-mediated atherosclerosis and ischemic heart disease.
authors.affiliation: Department of Epidemiology, Research Institute, National Cardiovascular Center, Suita, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yamawaki
authors.forename: Naoharu
authors.initials: N
authors.lastname: Iwai
mesh_terms: D000397:Air Pollution / Q000009:adverse effects*; D050197:Atherosclerosis / Q000503:physiopathology*; D002244:Carbon / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D049329:Nanostructures; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D014471:Umbilical Veins
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D002244:Carbon