title: Mononuclear cell therapy attenuates atherosclerosis in apoE KO mice.
abstract: BACKGROUND
  Recent studies have highlighted the potential of cell therapy for atherosclerosis. The aim of this study was to evaluate the effects of mononuclear cell (MNC) therapy on the development of atherosclerotic lesions in the apolipoprotein E knockout (apoE KO) mouse.
  
  
  METHODS
  We investigated vascular lipid deposition, vascular remodeling, oxidative stress, and endothelial nitric oxide synthase (eNOS) expression in apoE KO mice treated with spleen MNCs isolated from lacZ transgenic mice (apoE KO-MNC) for 8 weeks compared to untreated control mice (apoE KO).
  
  
  RESULTS
  Histological analysis of aortas showed a significant reduction in the lipid deposition area in apoE KO-MNC mice compared to apoE KO mice (0.051 ± 0.004 vs 0.117 ± 0.016 mm², respectively, p < 0.01). In addition, vessel morphometry revealed that MNC therapy prevented the outward (positive) remodeling in apoE KO mice that is normally observed (apoE KO-MNC: 0.98 ± 0.07 vs apoE KO: 1.37 ± 0.09), using wild-type mice (C57BL/6J) as a reference. ApoE KO-MNC mice also have reduced production of superoxide anions and increased eNOS expression compared to apoE KO mice. Finally, immunohistochemistry analysis revealed a homing of endothelial progenitor cells (EPCs) in the aortas of apoE KO-MNC mice.
  
  
  CONCLUSIONS
  MNC therapy attenuates the progression of atherosclerosis in the aortas of apoE KO mice. Our data provide evidence that the mechanism by which this attenuation occurs includes the homing of EPCs, a decrease in oxidative stress and an upregulation of eNOS expression.
authors: Laboratory of Transgenes and Cardiovascular Control, Dept Physiological Sciences, Health Sciences Center, Federal University of Espirito Santo, Vitoria, ES, Brazil.
authors: Marcella L
authors: ML
authors: Porto
authors: Leandro C F
authors: LC
authors: Lima
authors: Thiago M C
authors: TM
authors: Pereira
authors: Breno V
authors: BV
authors: Nogueira
authors: Clarissa L
authors: CL
authors: Tonini
authors: Bianca P
authors: BP
authors: Campagnaro
authors: Silvana S
authors: SS
authors: Meyrelles
authors: Elisardo C
authors: EC
authors: Vasquez
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D018450:Disease Progression; D005260:Female; D007150:Immunohistochemistry; D017708:Leukocyte Transfusion; D007963:Leukocytes, Mononuclear; D050356:Lipid Metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress; D058226:Plaque, Atherosclerotic / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D013234:Stem Cells / Q000473:pathology; D013481:Superoxides / Q000378:metabolism; D015854:Up-Regulation; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; D013481:Superoxides; D052250:Nitric Oxide Synthase Type III; D001616:beta-Galactosidase