Endothelial overexpression of fas ligand decreases atherosclerosis in apolipoprotein E-deficient mice

Jiang Yang, Kaori Sato, Tamar Aprahamian, Nathaniel J. Brown, Jack Hutcheson, Ann Bialik, Harris Perlman, Kenneth Walsh

Research output: Contribution to journalArticle

16 Citations (Scopus)

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. Methods and 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.

Original languageEnglish (US)
Pages (from-to)1466-1473
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume24
Issue number8
DOIs
StatePublished - Aug 2004

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Fas Ligand Protein
Apolipoproteins E
Atherosclerosis
Transgenic Mice
Thoracic Aorta
CD95 Antigens
Abdominal Aorta
High Fat Diet
Transgenes
Knockout Mice
Aorta
Triglycerides
Anti-Inflammatory Agents
Endothelial Cells
Macrophages
Cholesterol

Keywords

  • Atherosclerosis
  • Endothelium
  • Fas ligand
  • Inflammation
  • Transgene

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Endothelial overexpression of fas ligand decreases atherosclerosis in apolipoprotein E-deficient mice. / Yang, Jiang; Sato, Kaori; Aprahamian, Tamar; Brown, Nathaniel J.; Hutcheson, Jack; Bialik, Ann; Perlman, Harris; Walsh, Kenneth.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 24, No. 8, 08.2004, p. 1466-1473.

Research output: Contribution to journalArticle

Yang, J, Sato, K, Aprahamian, T, Brown, NJ, Hutcheson, J, Bialik, A, Perlman, H & Walsh, K 2004, 'Endothelial overexpression of fas ligand decreases atherosclerosis in apolipoprotein E-deficient mice', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 24, no. 8, pp. 1466-1473. https://doi.org/10.1161/01.ATV.0000134402.94963.2f
Yang, Jiang ; Sato, Kaori ; Aprahamian, Tamar ; Brown, Nathaniel J. ; Hutcheson, Jack ; Bialik, Ann ; Perlman, Harris ; Walsh, Kenneth. / Endothelial overexpression of fas ligand decreases atherosclerosis in apolipoprotein E-deficient mice. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2004 ; Vol. 24, No. 8. pp. 1466-1473.
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