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Fas/FADD-mediated activation of a specific program of inflammatory gene expression in vascular smooth muscle cells

Nature Medicine volume 6, pages 790–796 (2000)Cite this article

Abstract

Apoptosis of smooth muscle cells is a common feature of vascular lesions but its pathophysiological significance is not known. We demonstrate that signals initiated by regulated Fas-associated death domain protein overexpression in rat vascular smooth muscle cells in the carotid artery induce expression of monocyte-chemoattractant protein-1 and interleukin-8, and cause massive immigration of macrophages in vivo. These chemokines, and a specific set of other pro-inflammatory genes, are also upregulated in human vascular smooth muscle cells during Fas-induced apoptosis, in part through a process that requires interleukin-1α activation. Induction of a pro-inflammatory program by apoptotic vascular smooth muscle cells may thus contribute to the pathogenesis of vascular disease.

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Figure 1: Tet-regulation of FADD expression causes SMC apoptosis in culture and in vivo.
Figure 2: FADD expression results in recruitment of macrophages into the neointima.
Figure 3: FADD expression results in upregulation of MCP-1 and Il-8 transcript levels and activity.
Figure 4: Role of IL-1α and caspases in regulating MCP-1 expression.

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Acknowledgements

The authors thank M. Clowes, H. Lea and E. Mulvihill for instruction and advice. This work was supported by US Public Health Service grants HL03174 and HL62995 and by grants from the Deutsche Forschungsgemeinschaft and F. Hoffmann-La Roche.

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Authors and Affiliations

  1. Department of Pathology,, Box 357470

    Friedemann J. Schaub, David K.M. Han, Lawrence D. Adams, Scott A. Coats, Ravi K. Ramachandran, Ronald A. Seifert, Stephen M. Schwartz & Daniel F. Bowen-Pope

  2. University of Washington,, 98195-7470, Washington

    Friedemann J. Schaub, David K.M. Han, Lawrence D. Adams, Scott A. Coats, Ravi K. Ramachandran, Ronald A. Seifert, Stephen M. Schwartz & Daniel F. Bowen-Pope

  3. Department of Medicine,, Box 357185

    W. Conrad Liles

  4. University of Washington Seattle,, 98195-7185 , Washington

    W. Conrad Liles

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Correspondence to Daniel F. Bowen-Pope.

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Schaub, F., Han, D., Conrad Liles, W. et al. Fas/FADD-mediated activation of a specific program of inflammatory gene expression in vascular smooth muscle cells. Nat Med 6, 790–796 (2000). https://doi.org/10.1038/77521

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