Transforming growth factor-beta: a promising target for anti-stenosis therapy.
Transforming growth factor-beta (TGF-beta) is the general name for a family of cytokines which have widespread effects on many aspects of growth and development. The TGF-beta isoforms are produced by most cell types and exert a wide range of effects in a context-dependent autocrine, paracrine or endocrine fashion via interactions with distinct receptors on the cell surface. TGF-beta is involved in the wound healing process and, thus plays a significant role in the formation of a restenotic lesion after percutaneous transluminal coronary angioplasty (PTCA) or stenting. Perhaps because of its wide-ranging effects, TGF-beta is usually released from cells in a latent form, and its activation and signaling are complex. Manipulation of the TGF-beta1, TGF-beta2, and TGF-beta3 isoforms by inhibiting their expression, activation, or signaling reduces scarring and fibrosis in animal models. However, to date, few have reached clinical trial. This review summarizes current knowledge on the activation and signaling of TGF-beta, and focuses on the anti-TGF-beta strategies which may lead to clinical applications in the prevention of restenosis following PTCA or stenting.
Chamberlain
J
J
Cardiovascular Research Group, Section of Medicine, University of Sheffield, Clinical Sciences Centre, Northern General Hospital, Herries Road, Sheffield, S5 7AU, UK. j.chamberlain@sheffield.ac.uk
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D003251:Constriction, Pathologic / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D023903:Coronary Restenosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D058575:Decorin; D016503:Drug Delivery Systems / Q000379:methods; D016326:Extracellular Matrix Proteins; D066298:In Vitro Techniques; D008360:Mannosephosphates / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000502:physiology; D011498:Protein Precursors / Q000378:metabolism; D011509:Proteoglycans / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D015607:Stents / Q000009:adverse effects; D019700:Thrombospondin 1 / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000502:physiology*; D053773:Transforming Growth Factor beta1; D014945:Wound Healing / Q000502:physiology
D000906:Antibodies; D058575:Decorin; D016326:Extracellular Matrix Proteins; D008360:Mannosephosphates; D016376:Oligonucleotides, Antisense; D010446:Peptide Fragments; D020033:Protein Isoforms; D011498:Protein Precursors; D011509:Proteoglycans; D019700:Thrombospondin 1; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C027693:mannose-6-phosphate