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Troidl, Kerstin; Rüding, Inka; Cai, Wei-Jun; Mücke, Yvonne; Grossekettler, Leonie; Piotrowska, Izabela; Apfelbeck, Hanna; Schierling, Wilma; Volger, Oscar L.; Horrevoets, Anton J.; Grote, Karsten; Schmitz-Rixen, Thomas; Schaper, Wolfgang; Troidl, Christian

Actin-Binding Rho Activating Protein ( Abra ) Is Essential for Fluid Shear Stress-Induced Arteriogenesis

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  • Media type: E-Article
  • Title: Actin-Binding Rho Activating Protein ( Abra ) Is Essential for Fluid Shear Stress-Induced Arteriogenesis
  • Contributor: Troidl, Kerstin; Rüding, Inka; Cai, Wei-Jun; Mücke, Yvonne; Grossekettler, Leonie; Piotrowska, Izabela; Apfelbeck, Hanna; Schierling, Wilma; Volger, Oscar L.; Horrevoets, Anton J.; Grote, Karsten; Schmitz-Rixen, Thomas; Schaper, Wolfgang; Troidl, Christian
  • imprint: Ovid Technologies (Wolters Kluwer Health), 2009
  • Published in: Arteriosclerosis, Thrombosis, and Vascular Biology
  • Language: English
  • DOI: 10.1161/atvbaha.109.195305
  • ISSN: 1079-5642; 1524-4636
  • Keywords: Cardiology and Cardiovascular Medicine
  • Origination:
  • Footnote:
  • Description: <jats:p> <jats:bold> <jats:italic>Objective—</jats:italic> </jats:bold> 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 <jats:italic>actin-binding Rho activating protein</jats:italic> ( <jats:italic>Abra</jats:italic> ), which was highly upregulated in growing collaterals. </jats:p> <jats:p> <jats:bold> <jats:italic>Methods and Results—</jats:italic> </jats:bold> qRT-PCR and Western blot confirmed highly increased FSS-dependent expression of <jats:italic>Abra</jats:italic> in growing collaterals. NO blockage by L-NAME abolished FSS-generated <jats:italic>Abra</jats:italic> 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 <jats:italic>Abra</jats:italic> improved collateral conductance by 60% in rabbits compared to the natural response after FAL. In contrast, targeted deletion of <jats:italic>Abra</jats:italic> in CL57BL/6 mice led to impaired arteriogenesis. </jats:p> <jats:p> <jats:bold> <jats:italic>Conclusions—</jats:italic> </jats:bold> FSS-induced <jats:italic>Abra</jats:italic> expression during arteriogenesis is triggered by NO and leads to stimulation of collateral growth by smooth muscle cell proliferation. </jats:p>