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Titolo:
Restenosis following angioplasty in the swine coronary artery is inhibitedby an orally active PDGF-receptor tyrosine kinase inhibitor, RPR101511A
Autore:
Bilder, G; Wentz, T; Leadley, R; Amin, D; Byan, L; OConner, B; Needle, S; Galczenski, H; Bostwick, J; Kasiewski, C; Myers, M; Spada, A; Merkel, L; Ly, C; Persons, P; Page, K; Perrone, M; Dunwiddie, C;
Indirizzi:
Rhone Poulenc Rorer, Dept Cardiovasc Biol, Collegeville, PA 19426 USA Rhone Poulenc Rorer Collegeville PA USA 19426 Collegeville, PA 19426 USA Rhone Poulenc Rorer, Dept Med Chem, Collegeville, PA 19426 USA Rhone Poulenc Rorer Collegeville PA USA 19426 Collegeville, PA 19426 USA Rhone Poulenc Rorer, Dept Lab Anim Resources, Collegeville, PA 19426 USA Rhone Poulenc Rorer Collegeville PA USA 19426 Collegeville, PA 19426 USA Rhone Poulenc Rorer, Dept Drug Metab, Dagenham, Essex, England Rhone Poulenc Rorer Dagenham Essex England tab, Dagenham, Essex, England
Titolo Testata:
CIRCULATION
fascicolo: 25, volume: 99, anno: 1999,
pagine: 3292 - 3299
SICI:
0009-7322(19990629)99:25<3292:RFAITS>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
SMOOTH-MUSCLE CELLS; FACTOR-B CHAIN; BALLOON ANGIOPLASTY; MESSENGER-RNA; PROLIFERATION; ANGIOPEPTIN; PREVENTION; EXPRESSION; MIGRATION; PROBUCOL;
Keywords:
angioplasty; restenosis; platelet-derived factors;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Bilder, G Rhone Poulenc Rorer, Dept Cardiovasc Biol, NW4, Collegeville, PA19426 USA Rhone Poulenc Rorer NW4 Collegeville PA USA 19426 , PA 19426 USA
Citazione:
G. Bilder et al., "Restenosis following angioplasty in the swine coronary artery is inhibitedby an orally active PDGF-receptor tyrosine kinase inhibitor, RPR101511A", CIRCULATION, 99(25), 1999, pp. 3292-3299

Abstract

Background-Platelet-derived growth factor (PDGF), a purported mediator of arterial response to injury, stimulates proliferation, chemotaxis, and matrix production by activation of its membrane receptor tyrosine kinase. Because these activities underlie restenosis, inhibition of the PDGF-receptor tyrosine kinase (PDGFr-TK) is postulated to decrease restenosis,;Methods and Results-RPR101511A is a novel compound which selectively and potently inhibits the cell-free and in situ PDGFr-TK and PDGFr-dependent proliferation and chemotaxis in vascular smooth muscle cells (VSMC). To evaluate the effect of RPR101511A (30 mg.kg(-1).d(-1) BID for 28 days following PTCA) on coronary restenosis, PTCA was performed in hypercholesterolemic minipigs whose left anterior descending (LAD) coronary artery had been injuredby overdilation and denudation, yielding a previously existing lesion. Angiographically determined prePTCA minimal lumen diameters (MLD) were similarin vehicle and RPR101511A-treated pigs (1.98+/-0.09 versus 2.01+/-0.08 mm)and increased to the same extent in the 2 groups following successful PTCA(2.30+/-0.06 versus 2.52+/-0.13). At termination, there was an average 59%loss of gain in the vehicle-treated group but no loss of gain with RPR101511A (2.16+/-0.05 versus 2.59+/-0.11, P<0.001). Morphometric analysis of theLAD showed that RPR101511A caused a significant decrease in total intimal/medial ratio (0.96+/-0.58 versus 0.67+/-0.09, P<0.05). Conclusions-RPR101511A, which acts by inhibition of the PBGFr-TK, completely prevented angiographic loss of gain following PTCA and significantly reduced histological intimal hyperplasia.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/11/20 alle ore 13:55:15