title: Endothelial overexpression of Fas ligand decreases atherosclerosis in apolipoprotein E-deficient mice.
abstract: OBJECTIVE
  Fas ligand (FasL) can induce apoptosis in cells bearing the Fas receptor. The role of FasL in the vasculature with regard to atherosclerosis is controversial. This study examined the function of endothelial FasL during atherosclerosis.
  
  
  RESULTS
  Transgenic (Tg) mice that specifically overexpress different levels of FasL on vascular endothelial cells were crossed into the apolipoprotein E-knockout background (ApoE-KO) to generate ApoE-KO/FasL-Tg mice. Although plasma cholesterol and triglyceride levels were not different between ApoE-KO/FasL-Tg mice and ApoE-KO mice after 12 weeks of a high-fat diet, overexpression of the FasL transgene significantly reduced atherosclerotic lesion area in aortae by 49%. The reduction of atherosclerotic lesion area was more pronounced in thoracic and abdominal aortae than in the aortic arch, and a 34% reduction in lesion area was observed in aortic root sections from the ApoE-KO/FasL-Tg group compared with the ApoE-KO group. Immunostaining revealed significant decreases in both macrophage and CD8 T-cell accumulation in lesions of ApoE-KO/FasL-Tg mice. ApoE-KO/FasL-Tg mice that express lower levels of endothelial FasL also displayed reduced lesion size, but this reduction was statistically significant at the aortic arch only.
  
  
  CONCLUSIONS
  Overexpression of endothelial FasL is antiinflammatory and inhibits atherosclerosis under hypercholesterolemic conditions.
authors.affiliation: Department of Molecular Cardiology, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Mass 02118-2526, USA.
authors.forename: Jiang
authors.initials: J
authors.lastname: Yang
authors.forename: Kaori
authors.initials: K
authors.lastname: Sato
authors.forename: Tamar
authors.initials: T
authors.lastname: Aprahamian
authors.forename: Nathaniel J
authors.initials: NJ
authors.lastname: Brown
authors.forename: Jack
authors.initials: J
authors.lastname: Hutcheson
authors.forename: Ann
authors.initials: A
authors.lastname: Bialik
authors.forename: Harris
authors.initials: H
authors.lastname: Perlman
authors.forename: Kenneth
authors.initials: K
authors.lastname: Walsh
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism / Q000473:pathology; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D017209:Apoptosis; D001161:Arteriosclerosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004036:Diet, Atherogenic; D004730:Endothelium, Vascular / Q000378:metabolism*; D053222:Fas Ligand Protein; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation; D007958:Leukocyte Count; D008055:Lipids / Q000032:analysis; D008264:Macrophages / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D013602:T-Lymphocytes, Cytotoxic / Q000473:pathology
chemical_list: D001057:Apolipoproteins E; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008055:Lipids; D008562:Membrane Glycoproteins