| Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | Vascular Pharmacology | ||||
| Publisher: | ELSEVIER SCIENCE INC | ||||
| Place of Publication: | NEW YORK | ||||
| Volume: | 52 | ||||
| Number of Issue or Book Chapter: | 1-2 | ||||
| Page Range: | pp. 55-62 | ||||
| Date: | 2010 | ||||
| Institutions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical/Medicinal Chemistry I (Prof. Elz) | ||||
| Identification Number: |
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| Keywords: | DRUG-ELUTING STENTS; TYROSINE KINASE INHIBITOR; RAT CAROTID-ARTERY; REDUCES NEOINTIMA FORMATION; PORCINE CORONARY-ARTERIES; GROWTH-FACTOR; BALLOON ANGIOPLASTY; RANDOMIZED-TRIAL; LOCAL-DELIVERY; PREVENTION; Restenosis; Stent; PDGF; Bis(1H-2-indolyl)methanone; Rabbit | ||||
| Dewey Decimal Classification: | 600 Technology > 615 Pharmacy | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Yes | ||||
| Item ID: | 66653 |
Web of ScienceAbstract
Long-term success of modern therapies for myocardial ischemia is limited by restenosis. with proliferation and migration of vascular smooth muscle cells (VSMC) as key events. Since findings in recent years indicate, that the Platelet Derived Growth Factor (PDGF) is an important selective factor in mitogenic and motogenic pathways of VSMC, different concepts for reducing restenosis by inhibiting ...
Abstract
Long-term success of modern therapies for myocardial ischemia is limited by restenosis. with proliferation and migration of vascular smooth muscle cells (VSMC) as key events. Since findings in recent years indicate, that the Platelet Derived Growth Factor (PDGF) is an important selective factor in mitogenic and motogenic pathways of VSMC, different concepts for reducing restenosis by inhibiting PDGF signaling have been investigated, with local delivery of small receptor kinase inhibitors looking most promising. We tested the stent-based delivery of the PDGF-receptor inhibitor D-65495, a bis(1H-2-indolyl)methanone, in the rabbit iliac artery model of restenosis. New Zealand white rabbits underwent balloon dilation of iliac arteries for implantation of D-65495-coated or non-coated (solvent, either DMSO or 90%THF / 10% DMSO) coronary stents. After 4 weeks stents were removed and neointima formation in medial and proximal/ distal stent sections was histomorphometrically and immunohistochemically analyzed. Arteries with D-65495 eluting stents showed an up to 50% reduced restenosis compared to control stents. Also, the neointimal area was reduced, but there were no significant differences in injury score. Importantly, endothelialization was similar for control stents as well as for D-65495-coated stents, suggesting absence of a general cytostatic effect of the inhibitor. The impact of D-65495 on PDGF-receptor signaling in the vessel wall was indirectly assessed by immunohistochemical staining for activated protein kinase Akt, and PCNA as a proliferation marker and revealed some reduction for the inhibitor-treated vessels. In conclusion, the application of D-65495 caused a significant decrease in neointima formation, further supporting the concept of using locally released PDGF-receptor kinase inhibitors as anti-restenotic agents. (C) 2009 Elsevier Inc. All rights reserved.
Metadata last modified: 19 Dec 2024 11:48
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