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

2003; Wiley; Volume: 17; Issue: 10 Linguagem: Inglês

10.1096/fj.02-0814fje

1530-6860

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

Erythrocyte Function and Pathophysiology

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.