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



ID: 474460.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Publikationen des W. G. Kerckhoff-Instituts
Actin-binding rho activating protein (Abra) is essential for fluid shear stress-induced arteriogenesis
Authors:Troidl, K.; Ruding, I.; Cai, W. J.; Mucke, Y.; Grossekettler, L.; Piotrowska, I.; Apfelbeck, H.; Schierling, W.; Volger, O. L.; Horrevoets, A. J.; Grote, K.; Schmitz-Rixen, T.; Schaper, W.; Troidl, C.
Date of Publication (YYYY-MM-DD):2009
Title of Journal:Arterioscler Thromb Vasc Biol
Volume:29
Issue / Number:12
Start Page:2093
End Page:101
Audience:Not Specified
Abstract / Description:OBJECTIVE: Arteriogenesis, the development of a collateral circulation, is important for tissue survival but remains functionally defective because of early normalization of fluid shear stress (FSS). Using a surgical model of chronically elevated FSS we showed that rabbits exhibited normal blood flow reserve after femoral artery ligature (FAL). Inhibition of the Rho pathway by Fasudil completely blocked the beneficial effect of FSS. In a genome-wide gene profiling we identified actin-binding Rho activating protein (Abra), which was highly upregulated in growing collaterals. METHODS AND RESULTS: qRT-PCR and Western blot confirmed highly increased FSS-dependent expression of Abra in growing collaterals. NO blockage by L-NAME abolished FSS-generated Abra expression as well as the whole arteriogenic process. Cell culture studies demonstrated an Abra-triggered proliferation of smooth muscle cells through a mechanism that requires Rho signaling. Local intracollateral adenoviral overexpression of Abra improved collateral conductance by 60% in rabbits compared to the natural response after FAL. In contrast, targeted deletion of Abra in CL57BL/6 mice led to impaired arteriogenesis. CONCLUSIONS: FSS-induced Abra expression during arteriogenesis is triggered by NO and leads to stimulation of collateral growth by smooth muscle cell proliferation.
Free Keywords:Actins/metabolism; Adenoviridae/genetics; Animals; Arteries/*growth & development/*physiology; Cell Proliferation; Cells, Cultured; Collateral Circulation/physiology; Gene Transfer Techniques; Hemorheology; Mice; Mice, Knockout; Microfilament Proteins/deficiency/genetics/*metabolism; Myocytes, Smooth Muscle/cytology/metabolism; *Neovascularization, Physiologic; Rabbits; Rats; Rats, Sprague-Dawley; Signal Transduction; Swine; Up-Regulation; rho GTP-Binding Proteins/metabolism
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:Max-Planck-Institute for Heart and Lung Research, Parkstr. 1, D-61231 Bad Nauheim, Germany. kerstin.troidl@mpi-bn.mpg.de
Identifiers:ISSN:1524-4636 (Electronic) 1524-4636 (Linking)
URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=..
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