title: Adventitial vessel growth and progenitor cells activation in an ex vivo culture system mimicking human saphenous vein wall strain after coronary artery bypass grafting.
abstract: 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.
authors.affiliation: Unità di Ingegneria Tissutale, Centro Cardiologico Monzino, IRCCS, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Prandi
authors.affiliation: Politecnico di Milano, Dipartimento di Elettronica, Informazione e Bioingegneria, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Piola
authors.affiliation: Politecnico di Milano, Dipartimento di Elettronica, Informazione e Bioingegneria, Milan, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Soncini
authors.affiliation: Istituto di Patologia Medica, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Colussi
authors.affiliation: Unità di Immunologia e Genomica Funzionale, Centro Cardiologico Monzino, IRCCS, Milan, Italy.
authors.forename: Yuri
authors.initials: Y
authors.lastname: D'Alessandra
authors.affiliation: II Divisione di Cardiochirurgia, Centro Cardiologico Monzino, IRCCS, Milan, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Penza
authors.affiliation: Dipartimento di Scienze Cliniche e di Comunità, Università di Milano, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Agrifoglio
authors.affiliation: Unità di Ingegneria Tissutale, Centro Cardiologico Monzino, IRCCS, Milan, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Vinci
authors.affiliation: Dipartimento di Scienze Cliniche e di Comunità, Università di Milano, Milan, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Polvani
authors.affiliation: Division of Cardiovascular Epigenetics, Goethe University, Frankfurt-am-Main, Germany.
authors.forename: Carlo
authors.initials: C
authors.lastname: Gaetano
authors.affiliation: Politecnico di Milano, Dipartimento di Elettronica, Informazione e Bioingegneria, Milan, Italy.
authors.forename: Gianfranco Beniamino
authors.initials: GB
authors.lastname: Fiore
authors.affiliation: Unità di Ingegneria Tissutale, Centro Cardiologico Monzino, IRCCS, Milan, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pesce
mesh_terms: D063194:Adventitia / Q000254:growth & development*; D001696:Biomechanical Phenomena; D001775:Blood Circulation; D002478:Cells, Cultured; D003251:Constriction, Pathologic / Q000209:etiology; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D011183:Postoperative Complications / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012501:Saphenous Vein / Q000166:cytology* / Q000254:growth & development* / Q000378:metabolism / Q000502:physiology; D013234:Stem Cells / Q000166:cytology*; D013314:Stress, Mechanical
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger