Adventitial vessel growth and progenitor cells activation in an ex vivo culture system mimicking human saphenous vein wall strain after coronary artery bypass grafting

• Published in: PloS one Vol. 10; no. 2; p. e0117409
• Main Authors: Prandi, Francesca, Piola, Marco, Soncini, Monica, Colussi, Claudia, D'Alessandra, Yuri, Penza, Eleonora, Agrifoglio, Marco, Vinci, Maria Cristina, Polvani, Gianluca, Gaetano, Carlo, Fiore, Gianfranco Beniamino, Pesce, Maurizio
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17.02.2015; Public Library of Science (PLoS)
• Subjects: Activation; Adventitia - growth & development; Apoptosis; Arteriosclerosis; Atherosclerosis; Biological effects; Biology; Biomechanical Phenomena; Blood Circulation; Blood flow; Blood pressure; Blood vessels; Bone morphogenetic protein 2; CD44 antigen; Cell culture; Cell proliferation; Cells (biology); Cells, Cultured; Constriction, Pathologic - etiology; Coronary artery; Coronary artery bypass; Coronary Artery Bypass - adverse effects; Coronary vessels; Gene expression; Gene Expression Regulation; Grafting; Growth; Heart surgery; Humans; Ischemia; Low pressure; Metallography; MicroRNAs; MicroRNAs - genetics; Mimicry; miRNA; Muscles; Perfusion; Physiological aspects; Physiology; Postoperative Complications - genetics; Postoperative Complications - pathology; Postoperative Complications - physiopathology; Pressure effects; Progenitor cells; Proteases; Proteinase inhibitors; RNA, Messenger - genetics; RNA, Messenger - metabolism; Saphenous Vein - cytology; Saphenous Vein - growth & development; Saphenous Vein - metabolism; Saphenous Vein - physiology; Smooth muscle; Stem cells; Stem Cells - cytology; Stress, Mechanical; Surgery; Thrombosis; Transforming growth factor-b1; Veins & arteries; Italy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0117409

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.