title: Human Saphenous Vein Response to Trans-wall Oxygen Gradients in a Novel Ex Vivo Conditioning Platform.
abstract: Autologous saphenous veins are commonly used for the coronary artery bypass grafting even if they are liable to progressive patency reduction, known as 'vein graft disease'. Although several cellular and molecular causes for vein graft disease have been identified using in vivo models, the metabolic cues induced by sudden interruption of vasa vasorum blood supply have remained unexplored. In the present manuscript, we describe the design of an ex vivo culture system allowing the generation of an oxygen gradient between the luminal and the adventitial sides of the vein. This system featured a separation between the inner and the outer vessel culture circuits, and integrated a purpose-developed de-oxygenator module enabling the trans-wall oxygen distribution (high oxygen level at luminal side and low oxygen level at the adventitial side) existing in arterialized veins. Compared with standard cultures the bypass-specific conditions determined a significant increase in the proliferation of cells around adventitial vasa vasorum and an elevation in the length density of small and large caliber vasa vasorum. These results suggest, for the first time, a cause-effect relationship between the vein adventitial hypoxia and a neo-vascularization process, a factor known to predispose the arterialized vein conduits to restenosis.
authors: Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, P.zza Leonardo da Vinci 32, 20133, Milan, Italy. marco.piola@polimi.it.
authors: Marco
authors: M
authors: Piola
authors: Unità di Ingegneria Tissutale, Centro Cardiologico Monzino-IRCCS, Via Parea 4, 20138, Milan, Italy.
authors: Francesca
authors: F
authors: Prandi
authors: Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, P.zza Leonardo da Vinci 32, 20133, Milan, Italy.
authors: Gianfranco Beniamino
authors: GB
authors: Fiore
authors: Dipartimento di Scienze Cliniche e di Comunità, Università di Milano, Via Parea 4, 20138, Milan, Italy.
authors: Marco
authors: M
authors: Agrifoglio
authors: Dipartimento di Scienze Cliniche e di Comunità, Università di Milano, Via Parea 4, 20138, Milan, Italy.
authors: Gianluca
authors: G
authors: Polvani
authors: Unità di Ingegneria Tissutale, Centro Cardiologico Monzino-IRCCS, Via Parea 4, 20138, Milan, Italy.
authors: Maurizio
authors: M
authors: Pesce
authors: Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, P.zza Leonardo da Vinci 32, 20133, Milan, Italy.
authors: Monica
authors: M
authors: Soncini
mesh_terms: D005260:Female; D006801:Humans; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009924:Organ Culture Techniques; D010100:Oxygen / Q000378:metabolism*; D012501:Saphenous Vein / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D014651:Vasa Vasorum / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
chemical_list: D010100:Oxygen
keywords: Coronary artery bypass grafting; De-oxygenator system; Oxygen conditioning; Saphenous vein graft disease; Vessel culture system; neo-Vascularization