Work, L.M. , McPhaden, A.R., Pyne, N.J., Pyne, S., Wadsworth, R.M. and Wainwright, C.L. (2001) Short-term local delivery of an inhibitor of ras farnesyltransferase prevents neointima formation in vivo after porcine coronary balloon angioplasty. Circulation, 104(13), pp. 1538-1543. (doi: 10.1161/hc3801.095661)
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Publisher's URL: http://dx.doi.org/10.1161/hc3801.095661
Abstract
<b>Background</b> Mitogenic stimuli present at the site of coronary arterial balloon injury contribute to the progression and development of a restenotic lesion, many signaling through a common pathway involving the small G protein p21<sup>ras</sup>. Our aim was to demonstrate in biochemical studies that farnesyl protein transferase inhibitor III (FPTIII) is an inhibitor of p21<sup>ras</sup> processing and that when it is given locally in vivo at the site of coronary balloon injury in a porcine model, it can inhibit neointima formation.<p></p> <b>Methods and Results</b> FPTIII (1 to 25 μmol/L) concentration-dependently reduced p21<sup>ras</sup> levels in porcine coronary artery smooth muscle cell membranes. FPTIII also prevented p42/p44 MAPK activation and DNA synthesis in response to platelet-derived growth factor in these cells at a concentration of 25 μmol/L. Application of 25 μmol/L FPTIII locally for 15 minutes to balloon-injured porcine coronary arteries in vivo prevented neointima formation assessed at 4 weeks, reduced proteoglycan deposition, and inhibited adventitial hypertrophy. Coronary arteries from FPTIII-treated pigs had no deterioration in contraction or in endothelium-dependent relaxation.<p></p> <b>Conclusions</b> The study demonstrates in the pig that short-term local delivery of inhibitors of p21<sup>ras</sup>-dependent mitogenic signal transduction prevents restenosis after balloon angioplasty.<p></p>
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Work, Dr Lorraine |
Authors: | Work, L.M., McPhaden, A.R., Pyne, N.J., Pyne, S., Wadsworth, R.M., and Wainwright, C.L. |
College/School: | College of Medical Veterinary and Life Sciences College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
Journal Name: | Circulation |
ISSN: | 0009-7322 |
ISSN (Online): | 1524-4539 |
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