Renske J de Jong1, Nicole Paulin1, Patricia Lemnitzer1, Joana R Viola1, Carla Winter1, Bartolo Ferraro1, Jochen Grommes1, Christian Weber1, Chris Reutelingsperger1, Maik Drechsler1, Oliver Soehnlein2. 1. From the IPEK, LMU Munich, Germany (R.J.d.J., N.P., P.L., J.R.V., C. Winter, B.F., J.G., C. Weber, M.D., O.S.); Department of Pathology, AMC, Amsterdam University, The Netherlands (R.J.d.J., J.R.V., M.D., O.S.); Department of Experimental Medicine, Second University of Naples, Italy (B.F.); European Vascular Center Aachen-Maastricht, University Hospital RWTH Aachen, Germany (J.G.); Department of Biochemistry, CARIM, Maastricht University, The Netherlands (C. Weber, C.R.); and DZHK, partner site Munich Heart Alliance, Germany (C. Weber, M.D., O.S.). 2. From the IPEK, LMU Munich, Germany (R.J.d.J., N.P., P.L., J.R.V., C. Winter, B.F., J.G., C. Weber, M.D., O.S.); Department of Pathology, AMC, Amsterdam University, The Netherlands (R.J.d.J., J.R.V., M.D., O.S.); Department of Experimental Medicine, Second University of Naples, Italy (B.F.); European Vascular Center Aachen-Maastricht, University Hospital RWTH Aachen, Germany (J.G.); Department of Biochemistry, CARIM, Maastricht University, The Netherlands (C. Weber, C.R.); and DZHK, partner site Munich Heart Alliance, Germany (C. Weber, M.D., O.S.). oliver.soehnlein@gmail.com.
Abstract
OBJECTIVE: Restenosis as a consequence of arterial injury is aggravated by inflammatory pathways. Here, we investigate the role of the proresolving protein annexin A1 (AnxA1) in healing after wire injury. APPROACH AND RESULTS: Apoe-/- and Apoe-/-Anxa1-/- mice were subjected to wire injury while fed a high-cholesterol diet. Subsequently, localization of AnxA1 and AnxA1 plasma levels were examined. AnxA1 was found to localize within endothelial cells and macrophages in the neointima. Levels of AnxA1 in the plasma and its lesional expression negatively correlated with neointima size, and in the absence of AnxA1, neointima formation was aggravated by the accumulation and proliferation of macrophages. In contrast, reendothelialization and smooth muscle cell infiltration were not affected in Apoe-/-Anxa1-/- mice. CONCLUSIONS: AnxA1 is protective in healing after wire injury and could, therefore, be an attractive therapeutic compound to prevent from restenosis after vascular damage.
OBJECTIVE: Restenosis as a consequence of arterial injury is aggravated by inflammatory pathways. Here, we investigate the role of the proresolving protein annexin A1 (AnxA1) in healing after wire injury. APPROACH AND RESULTS: Apoe-/- and Apoe-/-Anxa1-/- mice were subjected to wire injury while fed a high-cholesterol diet. Subsequently, localization of AnxA1 and AnxA1 plasma levels were examined. AnxA1 was found to localize within endothelial cells and macrophages in the neointima. Levels of AnxA1 in the plasma and its lesional expression negatively correlated with neointima size, and in the absence of AnxA1, neointima formation was aggravated by the accumulation and proliferation of macrophages. In contrast, reendothelialization and smooth muscle cell infiltration were not affected in Apoe-/-Anxa1-/- mice. CONCLUSIONS: AnxA1 is protective in healing after wire injury and could, therefore, be an attractive therapeutic compound to prevent from restenosis after vascular damage.
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