The terminal complement complex inhibits apoptosis in vascular smooth muscle cells by activating an autocrine IGF-1 loop.

Thomas P. Zwaka, Jan Torzewski, Andreas Hoeflich, Marion Déjosez, Steffen Kaiser, Vinzenz Hombach, Peter M. Jehle

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

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.

Original languageEnglish
Pages (from-to)1346-1348
Number of pages3
JournalFASEB Journal
Volume17
Issue number10
DOIs
StatePublished - Jul 2003
Externally publishedYes

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