title: Acrolein inhalation prevents vascular endothelial growth factor-induced mobilization of Flk-1+/Sca-1+ cells in mice.
abstract: OBJECTIVE
  Acrolein is a toxic chemical present in tobacco, wood, and coal smoke, as well as automobile exhaust. Because exposure to these pollutants is associated with an increase in cardiovascular disease risk, we studied the effects of acrolein on Flk-1(+)/Sca-1(+) cells that are involved in vascular repair.
  
  
  RESULTS
  In adult male C57BL/6 mice, inhalation of acrolein (1 part per million [ppm], 6 hours/day for 4 days or 5 ppm for 2 or 6 hours) led to the formation of protein-acrolein adducts in the bone marrow and diminished levels of plasma nitric oxide metabolites and circulating Flk-1(+)/Sca-1(+) but not Sca-1(+)-only cells. Acrolein exposure increased the number of apoptotic Flk-1(+)/Sca-1(+) cells in circulation and increased bone marrow-derived cells with endothelial characteristics (DiI-ac-low-density lipoprotein [DiI-acLDL]/UE-lectin and Flk-1(+)/Sca-1(+)) in culture. Deficits in the circulating levels of Flk-1(+)/Sca-1(+) cells were reversed after 7 days of recovery in acrolein-free air. Exposure to acrolein blocked vascular endothelial growth factor (VEGF)/AMD3100-stimulated mobilization of Flk-1(+)/Sca-1(+) but not Sca-1(+)-only cells and prevented VEGF-induced phosphorylation of Akt and endothelial nitric oxide synthase in the aorta.
  
  
  CONCLUSIONS
  Inhalation of acrolein increases apoptosis and suppresses the circulating levels of Flk-1(+)/Sca-1(+) cells while increasing these cells in the bone marrow and preventing their mobilization by VEGF. Exposure to acrolein-rich pollutants could impair vascular repair capacity.
authors.affiliation: Diabetes and Obesity Center, Department of Physiology and Biophysics, University of Louisville, Louisville, KY 40292, USA.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Wheat
authors.forename: Petra
authors.initials: P
authors.lastname: Haberzettl
authors.forename: Jason
authors.initials: J
authors.lastname: Hellmann
authors.forename: Shahid P
authors.initials: SP
authors.lastname: Baba
authors.forename: Matthew
authors.initials: M
authors.lastname: Bertke
authors.forename: Jongmin
authors.initials: J
authors.lastname: Lee
authors.forename: James
authors.initials: J
authors.lastname: McCracken
authors.forename: Timothy E
authors.initials: TE
authors.lastname: O'Toole
authors.forename: Aruni
authors.initials: A
authors.lastname: Bhatnagar
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Conklin
mesh_terms: D000171:Acrolein / Q000008:administration & dosage / Q000633:toxicity*; D000393:Air Pollutants / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D001596:Benzylamines; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement; D002478:Cells, Cultured; D000080027:Cyclams; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006571:Heterocyclic Compounds / Q000494:pharmacology; D019570:Inhalation Exposure; D007279:Injections, Subcutaneous; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000097:blood; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010641:Phenotype; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D000393:Air Pollutants; D000950:Antigens, Ly; D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D009569:Nitric Oxide; D000171:Acrolein; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D040301:Vascular Endothelial Growth Factor Receptor-2; D051057:Proto-Oncogene Proteins c-akt; C088327:plerixafor