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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook_2014     Display Documents

ID: 682199.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook_2014
Effects of multikinase inhibitors on pressure overload-induced right ventricular remodeling
Authors:Kojonazarov, B.; Sydykov, A.; Pullamsetti, S. S.; Luitel, H.; Dahal, B. K.; Kosanovic, D.; Tian, X.; Majewski, M.; Baumann, C.; Evans, S.; Phillips, P.; Fairman, D.; Davie, N.; Wayman, C.; Kilty, I.; Weissmann, N.; Grimminger, F.; Seeger, W.; Ghofrani, H. A.; Schermuly, R. T.
Date of Publication (YYYY-MM-DD):2013-09-10
Journal Abbrev.:Int J Cardiol
Issue / Number:6
Start Page:2630
End Page:2637
Audience:Not Specified
Abstract / Description:BACKGROUND: Little is known about the effects of current PAH therapies and receptor tyrosine kinase inhibitors on heart remodeling. We sought to investigate the effects of the multikinase inhibitors sunitinib (PDGFR-, VEGFR- and KIT-inhibitor) and sorafenib (raf1/b-, VEGFR-, PDGFR-inhibitor) on pressure overload induced right ventricular (RV) remodeling. METHODS: We investigated the effects of the kinase inhibitors on hemodynamics and remodeling in rats subjected either to monocrotaline (MCT)-induced PH or to surgical pulmonary artery banding (PAB). MCT rats were treated from days 21 to 35 with either vehicle, sunitinib (1mg/kg, 5mg/kg and 10mg/kg/day) or sorafenib (10mg/kg/day). PAB rats were treated with vehicle, sunitinib (10mg/kg/day) or sorafenib (10mg/kg/day) from days 7 to 21. RV function and remodeling were determined using echocardiography, invasive hemodynamic measurement and histomorphometry. RESULTS: Treatment with both sorafenib and sunitinib decreased right ventricular systolic pressure, pulmonary vascular remodeling, RV hypertrophy and fibrosis in MCT rats. This was associated with an improvement of RV function. Importantly, after PAB, both compounds reversed RV chamber and cellular hypertrophy, reduced RV interstitial and perivascular fibrosis, and improved RV function. CONCLUSION: We demonstrated that sunitinib and sorafenib reversed RV remodeling and significantly improved RV function measured via a range of invasive and non-invasive cardiopulmonary endpoints in experimental models of RV hypertrophy.
External Publication Status:published
Document Type:Article
Communicated by:Svea Hümmer
Affiliations:MPI für physiologische und klinische Forschung
Identifiers:ISSN:1874-1754 (Electronic) 0167-5273 (Linking) %R 10.1016/j.ijcard.2012.06.129
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