An exochelin of Mycobacterium tuberculosis reversibly arrests growth of human vascular smooth muscle cells in vitro

Proliferation of vascular smooth muscle cells (VSMC) is characteristic of r estenosis following balloon angioplasty. We show here that a low concentrat ion of a novel iron chelator, desferri-exochelin 772SM, reversibly arrests the growth of human VSMC in vitro, specifically in G(0)/G(1) and S phases. The lipophilic desferri-exochelin is effective more rapidly and at a 10-fol d lower concentration than the nonlipophilic iron chelator deferoxamine. Tr eatment of growth-synchronized VSMC with the desferri-exochelin results in down-regulation of cyclin E/Cdk2 and cyclin A/Cdk2 activity but does not af fect the cyclin D/Cdk4/retinoblastoma phosphorylation pathway. Both DNA rep lication and RNA transcription are inhibited in exochelin-treated cells, bu t protein synthesis is not. The ability of desferri-exochelin 772SM to reve rsibly block the growth of VSMC in vitro with no apparent cytotoxicity sugg ests that the exochelin may be useful as a therapeutic agent to limit reste nosis in injured vessels.