title: Fas/FADD-mediated activation of a specific program of inflammatory gene expression in vascular smooth muscle cells.
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-1alpha activation. Induction of a pro-inflammatory program by apoptotic vascular smooth muscle cells may thus contribute to the pathogenesis of vascular disease.
authors.affiliation: Department of Pathology, Box 357470, University of Washington, Washington 98195-7470, USA.
authors.forename: F J
authors.initials: FJ
authors.lastname: Schaub
authors.forename: D K
authors.initials: DK
authors.lastname: Han
authors.forename: W C
authors.initials: WC
authors.lastname: Liles
authors.forename: L D
authors.initials: LD
authors.lastname: Adams
authors.forename: S A
authors.initials: SA
authors.lastname: Coats
authors.forename: R K
authors.initials: RK
authors.lastname: Ramachandran
authors.forename: R A
authors.initials: RA
authors.lastname: Seifert
authors.forename: S M
authors.initials: SM
authors.lastname: Schwartz
authors.forename: D F
authors.initials: DF
authors.lastname: Bowen-Pope
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis; D002339:Carotid Arteries / Q000276:immunology / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism; D018932:Chemokine CCL2 / Q000096:biosynthesis; D053200:Fas-Associated Death Domain Protein; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D007375:Interleukin-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis; D009131:Muscle, Smooth, Vascular / Q000276:immunology*; D051381:Rats; D011916:Rats, Inbred F344; D015854:Up-Regulation; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018932:Chemokine CCL2; C505533:FADD protein, human; C505535:Fadd protein, rat; D053200:Fas-Associated Death Domain Protein; D007375:Interleukin-1; D016209:Interleukin-8; D019014:fas Receptor; D020169:Caspases