Restenosis Following Angioplasty in the Swine Coronary Artery Is Inhibited By an Orally Active PDGF-Receptor Tyrosine Kinase Inhibitor, RPR101511A
| العنوان: | Restenosis Following Angioplasty in the Swine Coronary Artery Is Inhibited By an Orally Active PDGF-Receptor Tyrosine Kinase Inhibitor, RPR101511A |
|---|---|
| المؤلفون: | Robert J. Leadley, Charles Kasiewski, Tara Wentz, Glenda E. Bilder, Jeffery Bostwick, Mark H. Perrone, Saul J. Needle, Betsey O’Conner, Christopher T. Dunwiddie, Lisa Byan, Kenneth Page, Helen Galczenski, Linda Merkel, Persons Paul E, Myers Michael R, Alfred P. Spada, Amin Dilip, Cuong Ly |
| المصدر: | Circulation. 99:3292-3299 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 1999. |
| سنة النشر: | 1999 |
| مصطلحات موضوعية: | Pathology, medicine.medical_specialty, Time Factors, Vascular smooth muscle, Platelet-derived growth factor, Swine, Administration, Oral, Coronary Disease, Thiophenes, Pharmacology, chemistry.chemical_compound, Restenosis, Recurrence, Cell surface receptor, Quinoxalines, Physiology (medical), medicine, Animals, Receptors, Platelet-Derived Growth Factor, Angioplasty, Balloon, Coronary, Enzyme Inhibitors, Tyrosine, biology, business.industry, Chemotaxis, Protein-Tyrosine Kinases, medicine.disease, chemistry, biology.protein, Tunica Intima, Tunica Media, Cardiology and Cardiovascular Medicine, business, Tyrosine kinase, Platelet-derived growth factor receptor |
| الوصف: | 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 injured by overdilation and denudation, yielding a previously existing lesion. Angiographically determined prePTCA minimal lumen diameters (MLD) were similar in 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 50% 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 P Conclusions —RPR101511A, which acts by inhibition of the PDGFr-TK, completely prevented angiographic loss of gain following PTCA and significantly reduced histological intimal hyperplasia. |
| تدمد: | 1524-4539 0009-7322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::65d180846942468a5df5011431ca5416 https://doi.org/10.1161/01.cir.99.25.3292 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....65d180846942468a5df5011431ca5416 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244539 00097322 |
|---|