title: Vein graft thrombi, a niche for smooth muscle cell colonization - a hypothesis to explain the asymmetry of intimal hyperplasia.
abstract: Essentials Vein graft failure is the most frequent late onset complication of coronary artery bypass grafting. Cuff technique-based interposition mouse model including new anticoagulation regime was conducted. Early vein graft thrombi may serve as a niche for smooth muscle cell colonization. The focal character of early thrombi may form the basis for the asymmetry of intimal hyperplasia.
  
  
  
  Background Autologous saphenous veins are widely used in coronary artery bypass grafting; however, 10 years after surgery, 40% of grafts are completely occluded, and another 30% show reduced blood flow. Objective In the past, the central processes and signaling pathways responsible for this loss of patency have been identified. However, one central finding in the process of graft failure is so far not understood: the asymmetric character of intimal hyperplasia. It was the goal of the present study to address this aspect. Methods By the use of a cuff technique-based vein interposition mouse model with a new anticoagulation regime, alterations in vein grafts were analyzed 1 h, 1 day, 2 days, 3 days, 7 days and 21 days after reperfusion by means of immunolabeling, histochemistry, and high-resolution ultrasound. Results The novel and major finding of this study is that the vein graft thrombus may serve as a niche that is infiltrated and colonized by smooth muscle cells (SMCs). Fibroblast growth factor-1 and platelet-derived growth factor-B may be the SMC-attracting factors in the thrombus. The focal character of early thrombi may define the focal and asymmetric character of vein graft intimal hyperplasia. Conclusions Inhibiting the formation and reducing the size of early thrombi is an old concept for reducing vein graft failure. However, in light of the present new findings obtained under a clinic-like anticoagulation regime, early vein graft thrombus prevention/size reduction should be revisited in the prevention of graft failure.
authors.affiliation: Cardiac Surgery Research Laboratory, University Clinic for Cardiac Surgery, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: I
authors.initials: I
authors.lastname: Blaas
authors.affiliation: Cardiac Surgery Research Laboratory, University Clinic for Cardiac Surgery, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: K
authors.initials: K
authors.lastname: Heinz
authors.affiliation: Institute of Medical and Chemical Laboratory Diagnostics (ZIMCL), Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: P
authors.initials: P
authors.lastname: Würtinger
authors.affiliation: Cardiac Surgery Research Laboratory, Department of Cardiac Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Türkcan
authors.affiliation: Cardiac Surgery Research Laboratory, University Clinic for Cardiac Surgery, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Tepeköylü
authors.affiliation: Cardiac Surgery Research Laboratory, University Clinic for Cardiac Surgery, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Grimm
authors.affiliation: Cardiac Surgery Research Laboratory, University Clinic for Cardiac Surgery, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Doppler
authors.affiliation: Cardiac Surgery Research Laboratory, University Clinic for Cardiac Surgery, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: K
authors.initials: K
authors.lastname: Danzl
authors.affiliation: Cardiac Surgery Research Laboratory, Department of Cardiac Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: B
authors.initials: B
authors.lastname: Messner
authors.affiliation: Cardiac Surgery Research Laboratory, University Clinic for Cardiac Surgery, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: D
authors.initials: D
authors.lastname: Bernhard
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000737:chemistry* / Q000627:therapeutic use; D001783:Blood Flow Velocity; D001026:Coronary Artery Bypass; D004730:Endothelium, Vascular; D006965:Hyperplasia / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000378:metabolism; D015424:Reperfusion; D012501:Saphenous Vein / Q000637:transplantation*; D015398:Signal Transduction; D013927:Thrombosis / Q000473:pathology; D014463:Ultrasonography
chemical_list: D000925:Anticoagulants
keywords: coronary artery bypass grafting; etiology; thrombosis; vascular graft restenosis; venous intima