Adventitial Vessel Growth and Progenitor Cells Activation in an Ex Vivo Culture System Mimicking Human Saphenous Vein Wall Strain after Coronary Artery Bypass Grafting

• DOI: 10.1371/journal.pone.0117409
• Publication Date: 2015-02-17T19:04:25Z
• Authors: Francesca Prandi; Marco Piola; Monica Soncini; Claudia Colussi; Yuri D’Alessandra; Eleonora Penza; Marco Agrifoglio; Maria Cristina Vinci; Gianluca Polvani; Carlo Gaetano; Gianfranco Beniam...; Maurizio Pesce
• Keywords: 0301 basic medicine; Adventitia; Science; 610; Constriction, Pathologic; 03 medical and health sciences; endothelium epigentics; Postoperative Complications; Humans; Saphenous Vein; ddc:610; Agricultural and Biological Sciences (all); Biochemistry, Genetics and Molecular Biology (all); Medicine (all); RNA, Messenger; Coronary Artery Bypass; Cells, Cultured; ddc:610; Stem Cells; Q; R; Biomechanical Phenomena; MicroRNAs; Gene Expression Regulation; Blood Circulation; Medicine; Stress, Mechanical; Research Article

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.