Overexpression of soluble Fas attenuates transplant arteriosclerosis in rat aortic allografts

Tao Wang, Chunming Dong, Susan C. Stevenson, Edward E. Herderick, Jennifer Marshall-Neff, Sanjay S. Vasudevan, Nicanor I. Moldovan, Robert E. Michler, N. Rao Movva, Pascal J. Goldschmidt-Clermont

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Background - The killing of vascular cells by activated macrophages is an important step in the process of destabilization of the arterial wall. The death receptor Fas is implicated in vascular cell death. Hence, we extended our studies in a rat aortic allograft model, using adenovirus-mediated overexpression of soluble Fas (sFas) to block Fas binding to Fas ligand (Fas-L). The contribution of Fas to vascular cell injury and consequent transplant arteriosclerosis was investigated. Methods and Results - Activated monocytes in the presence of macrophage colony-stimulating factor induce endothelial cell apoptosis in vitro, which was significantly inhibited by adenovirus-mediated sFas overexpression. Next, donor rat abdominal aortas were either untreated or transduced with adenoviruses encoding (1) rat soluble Fas (Ad3rsFas), (2) no insert (Ad3Null), and (3) β-galactosidase (Ad3nBg). A total of 175 aortic grafts were harvested 2 to 90 days after transplantation. Vascular cell apoptosis and CD45+ cell infiltration were significantly reduced in Ad3rsFas-transduced aortas, as compared with control allografts. Moreover, the control allografts developed marked intimal thickening, whereas Ad3rsFas-transduced allografts had significantly less neointima until the 90-day time point. Conclusions - sFas overexpression protects the integrity of the vessel wall from immune injury and attenuates transplant arteriosclerosis.

Original languageEnglish (US)
Pages (from-to)1536-1542
Number of pages7
JournalCirculation
Volume106
Issue number12
DOIs
StatePublished - Sep 17 2002
Externally publishedYes

Fingerprint

Arteriosclerosis
Allografts
Adenoviridae
Transplants
Blood Vessels
Galactosidases
Tunica Intima
Apoptosis
Neointima
Death Domain Receptors
Fas Ligand Protein
Macrophage Colony-Stimulating Factor
Vascular System Injuries
Abdominal Aorta
Aorta
Monocytes
Cell Death
Endothelial Cells
Transplantation
Macrophages

Keywords

  • Apoptosis
  • Arteriosclerosis
  • Endothelium
  • Gene therapy
  • Inflammation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Wang, T., Dong, C., Stevenson, S. C., Herderick, E. E., Marshall-Neff, J., Vasudevan, S. S., ... Goldschmidt-Clermont, P. J. (2002). Overexpression of soluble Fas attenuates transplant arteriosclerosis in rat aortic allografts. Circulation, 106(12), 1536-1542. https://doi.org/10.1161/01.CIR.0000027822.23269.07

Overexpression of soluble Fas attenuates transplant arteriosclerosis in rat aortic allografts. / Wang, Tao; Dong, Chunming; Stevenson, Susan C.; Herderick, Edward E.; Marshall-Neff, Jennifer; Vasudevan, Sanjay S.; Moldovan, Nicanor I.; Michler, Robert E.; Movva, N. Rao; Goldschmidt-Clermont, Pascal J.

In: Circulation, Vol. 106, No. 12, 17.09.2002, p. 1536-1542.

Research output: Contribution to journalArticle

Wang, T, Dong, C, Stevenson, SC, Herderick, EE, Marshall-Neff, J, Vasudevan, SS, Moldovan, NI, Michler, RE, Movva, NR & Goldschmidt-Clermont, PJ 2002, 'Overexpression of soluble Fas attenuates transplant arteriosclerosis in rat aortic allografts', Circulation, vol. 106, no. 12, pp. 1536-1542. https://doi.org/10.1161/01.CIR.0000027822.23269.07
Wang T, Dong C, Stevenson SC, Herderick EE, Marshall-Neff J, Vasudevan SS et al. Overexpression of soluble Fas attenuates transplant arteriosclerosis in rat aortic allografts. Circulation. 2002 Sep 17;106(12):1536-1542. https://doi.org/10.1161/01.CIR.0000027822.23269.07
Wang, Tao ; Dong, Chunming ; Stevenson, Susan C. ; Herderick, Edward E. ; Marshall-Neff, Jennifer ; Vasudevan, Sanjay S. ; Moldovan, Nicanor I. ; Michler, Robert E. ; Movva, N. Rao ; Goldschmidt-Clermont, Pascal J. / Overexpression of soluble Fas attenuates transplant arteriosclerosis in rat aortic allografts. In: Circulation. 2002 ; Vol. 106, No. 12. pp. 1536-1542.
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AU - Dong, Chunming

AU - Stevenson, Susan C.

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AU - Marshall-Neff, Jennifer

AU - Vasudevan, Sanjay S.

AU - Moldovan, Nicanor I.

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N2 - Background - The killing of vascular cells by activated macrophages is an important step in the process of destabilization of the arterial wall. The death receptor Fas is implicated in vascular cell death. Hence, we extended our studies in a rat aortic allograft model, using adenovirus-mediated overexpression of soluble Fas (sFas) to block Fas binding to Fas ligand (Fas-L). The contribution of Fas to vascular cell injury and consequent transplant arteriosclerosis was investigated. Methods and Results - Activated monocytes in the presence of macrophage colony-stimulating factor induce endothelial cell apoptosis in vitro, which was significantly inhibited by adenovirus-mediated sFas overexpression. Next, donor rat abdominal aortas were either untreated or transduced with adenoviruses encoding (1) rat soluble Fas (Ad3rsFas), (2) no insert (Ad3Null), and (3) β-galactosidase (Ad3nBg). A total of 175 aortic grafts were harvested 2 to 90 days after transplantation. Vascular cell apoptosis and CD45+ cell infiltration were significantly reduced in Ad3rsFas-transduced aortas, as compared with control allografts. Moreover, the control allografts developed marked intimal thickening, whereas Ad3rsFas-transduced allografts had significantly less neointima until the 90-day time point. Conclusions - sFas overexpression protects the integrity of the vessel wall from immune injury and attenuates transplant arteriosclerosis.

AB - Background - The killing of vascular cells by activated macrophages is an important step in the process of destabilization of the arterial wall. The death receptor Fas is implicated in vascular cell death. Hence, we extended our studies in a rat aortic allograft model, using adenovirus-mediated overexpression of soluble Fas (sFas) to block Fas binding to Fas ligand (Fas-L). The contribution of Fas to vascular cell injury and consequent transplant arteriosclerosis was investigated. Methods and Results - Activated monocytes in the presence of macrophage colony-stimulating factor induce endothelial cell apoptosis in vitro, which was significantly inhibited by adenovirus-mediated sFas overexpression. Next, donor rat abdominal aortas were either untreated or transduced with adenoviruses encoding (1) rat soluble Fas (Ad3rsFas), (2) no insert (Ad3Null), and (3) β-galactosidase (Ad3nBg). A total of 175 aortic grafts were harvested 2 to 90 days after transplantation. Vascular cell apoptosis and CD45+ cell infiltration were significantly reduced in Ad3rsFas-transduced aortas, as compared with control allografts. Moreover, the control allografts developed marked intimal thickening, whereas Ad3rsFas-transduced allografts had significantly less neointima until the 90-day time point. Conclusions - sFas overexpression protects the integrity of the vessel wall from immune injury and attenuates transplant arteriosclerosis.

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