1. An exochelin of Mycobacterium tuberculosis reversibly arrests growth of human vascular smooth muscle cells in vitro.
- Author
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Pahl, PM, Yan, XD, Hodges, YK, Rosenthal, EA, Horwitz, MA, and Horwitz, LD
- Subjects
Muscle ,Smooth ,Vascular ,Aorta ,Iliac Artery ,Saphenous Vein ,Cells ,Cultured ,Humans ,Mycobacterium tuberculosis ,Ferric Compounds ,Deferoxamine ,Peptides ,Cyclic ,Epidermal Growth Factor ,Cyclin-Dependent Kinases ,CDC2-CDC28 Kinases ,Cyclin E ,Retinoblastoma Protein ,Iron Chelating Agents ,Cell Cycle ,Cell Division ,Phosphorylation ,Dose-Response Relationship ,Drug ,Kinetics ,Cyclin-Dependent Kinase 2 ,Protein Serine-Threonine Kinases ,Atherosclerosis ,Aetiology ,2.1 Biological and endogenous factors ,Cardiovascular ,Good Health and Well Being ,Chemical Sciences ,Biological Sciences ,Medical and Health Sciences ,Biochemistry & Molecular Biology - Abstract
Proliferation of vascular smooth muscle cells (VSMC) is characteristic of restenosis following balloon angioplasty. We show here that a low concentration 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-fold lower concentration than the nonlipophilic iron chelator deferoxamine. Treatment of growth-synchronized VSMC with the desferri-exochelin results in down-regulation of cyclin E/ Cdk2 and cyclin A/Cdk2 activity but does not affect the cyclin D/Cdk4/retinoblastoma phosphorylation pathway. Both DNA replication and RNA transcription are inhibited in exochelin-treated cells, but protein synthesis is not. The ability of desferri-exochelin 772SM to reversibly block the growth of VSMC in vitro with no apparent cytotoxicity suggests that the exochelin may be useful as a therapeutic agent to limit restenosis in injured vessels.
- Published
- 2000