title: The terminal complement complex inhibits apoptosis in vascular smooth muscle cells by activating an autocrine IGF-1 loop.
abstract: Two counteracting processes determine accumulation of human vascular smooth muscle cells (SMCs) in atherosclerotic lesions: cell proliferation and apoptosis. SMCs synthesize insulin-like growth factor-1 (IGF-1), which potently inhibits apoptosis. The terminal complement complex C5b-9 interacts with SMCs in early human atherogenesis. In this study, we investigated whether C5b-9 may activate the IGF-1 system in SMCs, resulting in the inhibition of SMC apoptosis. C5b-9 generation on SMCs in vitro markedly reduced CD95-mediated apoptosis as assessed by flowcytometric analysis of annexin V binding and in caspase 3 assays. C5b-9 induced both significant IGF-1 release and up-regulation of IGF-1 binding sites in SMCs. Immunoneutralization of IGF-1 with a monoclonal IGF-1 antibody abolished the antiapoptotic effects of C5b-9. We conclude that C5b-9 inhibits apoptosis in SMCs by inducing an autocrine IGF-1 loop. This mechanism may contribute to the accumulation of SMCs in early human atherosclerotic lesions.
authors.affiliation: Department of Internal Medicine II, University of Ulm, Germany.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Zwaka
authors.forename: Jan
authors.initials: J
authors.lastname: Torzewski
authors.forename: Andreas
authors.initials: A
authors.lastname: Hoeflich
authors.forename: Marion
authors.initials: M
authors.lastname: Déjosez
authors.forename: Steffen
authors.initials: S
authors.lastname: Kaiser
authors.forename: Vinzenz
authors.initials: V
authors.lastname: Hombach
authors.forename: Peter M
authors.initials: PM
authors.lastname: Jehle
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D019898:Autocrine Communication; D001665:Binding Sites; D015938:Complement Membrane Attack Complex / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D014466:Ultraviolet Rays; D015854:Up-Regulation; D019014:fas Receptor / Q000378:metabolism
chemical_list: D015938:Complement Membrane Attack Complex; D019014:fas Receptor; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1