Prevention of Cardiac Allograft Arteriosclerosis by Protein Tyrosine Kinase Inhibitor Selective for Platelet-Derived Growth Factor Receptor

摘要: Background—Increased immunoreactivity of platelet-derived growth factor (PDGF)-AA, -Rα, and -Rβ in intimal cells correlates with the development cardiac allograft arteriosclerosis, a condition for which there is little or no current therapy. Therefore, we hypothesized that PDGF may have rate-limiting role this disease. Methods Results—The hypothesis was tested rat model heterotopic aortic allografts using dark agouti (AG-B4, RT1a) donors Wistar-Furth (AG-B2, RT1u) recipients. The recipients received CGP 53716, selective PDGF-R protein tyrosine kinase inhibitor, 50 mg · kg−1 d−1, vehicle 60 days. Cardiac also background cyclosporin A immunosuppression. Our results demonstrate 53716 significantly reduced incidence intensity arteriosclerotic lesions When coronary smooth muscle were stimulated vitro PDGF-AA -BB presence ...