TY - JOUR A1 - Prandi, Francesca A1 - Piola, Marco A1 - Soncini, Monica A1 - Colussi, Claudia A1 - Alessandra, Yuri d' A1 - Penza, Eleonora A1 - Agrifoglio, Marco A1 - Vinci, Maria Cristina A1 - Polvani, Gianluca A1 - Gaetano, Carlo A1 - Fiore, Gianfranco Beniamino A1 - Pesce, Maurizio T1 - Adventitial vessel growth and progenitor cells activation in an ex vivo culture system mimicking human saphenous vein wall strain after coronary artery bypass graftin T2 - PLoS One N2 - Saphenous vein graft disease is a timely problem in coronary artery bypass grafting. Indeed, after exposure of the vein to arterial blood flow, a progressive modification in the wall begins, due to proliferation of smooth muscle cells in the intima. As a consequence, the graft progressively occludes and this leads to recurrent ischemia. In the present study we employed a novel ex vivo culture system to assess the biological effects of arterial-like pressure on the human saphenous vein structure and physiology, and to compare the results to those achieved in the presence of a constant low pressure and flow mimicking the physiologic vein perfusion. While under both conditions we found an activation of Matrix Metallo-Proteases 2/9 and of microRNAs-21/146a/221, a specific effect of the arterial-like pressure was observed. This consisted in a marked geometrical remodeling, in the suppression of Tissue Inhibitor of Metallo-Protease-1, in the enhanced expression of TGF-β1 and BMP-2 mRNAs and, finally, in the upregulation of microRNAs-138/200b/200c. In addition, the veins exposed to arterial-like pressure showed an increase in the density of the adventitial vasa vasorum and of cells co-expressing NG2, CD44 and SM22α markers in the adventitia. Cells with nuclear expression of Sox-10, a transcription factor characterizing multipotent vascular stem cells, were finally found in adventitial vessels. Our findings suggest, for the first time, a role of arterial-like wall strain in the activation of pro-pathologic pathways resulting in adventitial vessels growth, activation of vasa vasorum cells, and upregulation of specific gene products associated to vascular remodeling and inflammation. Y1 - 2015 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/37171 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-371710 SN - 1932-6203 N1 - Copyright: © 2015 Prandi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited VL - 10 IS - (2): e0117409 PB - PLoS CY - Lawrence, Kan. ER -