title: Role of Excessive Autophagy Induced by Mechanical Overload in Vein Graft Neointima Formation: Prediction and Prevention.
abstract: Little is known regarding the interplays between the mechanical and molecular bases for vein graft restenosis. We elucidated the stenosis initiation using a high-frequency ultrasonic (HFU) echogenicity platform and estimated the endothelium yield stress from von-Mises stress computation to predict the damage locations in living rats over time. The venous-arterial transition induced the molecular cascades for autophagy and apoptosis in venous endothelial cells (ECs) to cause neointimal hyperplasia, which correlated with the high echogenicity in HFU images and the large mechanical stress that exceeded the yield strength. The ex vivo perfusion of arterial laminar shear stress to isolated veins further confirmed the correlation. EC damage can be rescued by inhibiting autophagy formation using 3-methyladenine (3-MA). Pretreatment of veins with 3-MA prior to grafting reduced the pathological increases of echogenicity and neointima formation in rats. Therefore, this platform provides non-invasive temporal spatial measurement and prediction of restenosis after venous-arterial transition as well as monitoring the progression of the treatments.
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ya-Ju
authors.initials: YJ
authors.lastname: Chang
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Hui-Chun
authors.initials: HC
authors.lastname: Huang
authors.affiliation: Division of Plastic Surgery, National Cheng Kung University Hospital, Tainan, Taiwan.
authors.forename: Yuan-Yu
authors.initials: YY
authors.lastname: Hsueh
authors.affiliation: Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Shao-Wei
authors.initials: SW
authors.lastname: Wang
authors.affiliation: Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan.|Medical Device Innovation Center, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Fong-Chin
authors.initials: FC
authors.lastname: Su
authors.affiliation: Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan.|Medical Device Innovation Center, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chih-Han
authors.initials: CH
authors.lastname: Chang
authors.affiliation: Department of Physiology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ming-Jer
authors.initials: MJ
authors.lastname: Tang
authors.affiliation: Institute of Engineering in Medicine, University of California, San Diego, CA92093, USA.
authors.forename: Yi-Shuan
authors.initials: YS
authors.lastname: Li
authors.affiliation: Department of Computational Science, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Shyh-Hau
authors.initials: SH
authors.lastname: Wang
authors.affiliation: Department of Biomedical Engineering, University of Southern California, Los Angeles, CA90089, USA.
authors.forename: Kirk K
authors.initials: KK
authors.lastname: Shung
authors.affiliation: Institute of Engineering in Medicine, University of California, San Diego, CA92093, USA.
authors.forename: Shu
authors.initials: S
authors.lastname: Chien
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.|Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan.|Medical Device Innovation Center, National Cheng Kung University, Tainan, Taiwan.|International Research Center for Wound Regeneration and Repair, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chia-Ching
authors.initials: CC
authors.lastname: Wu
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001158:Arteries / Q000601:surgery; D001343:Autophagy / Q000502:physiology*; D042783:Endothelial Cells / Q000473:pathology; D006083:Graft Occlusion, Vascular / Q000473:pathology / Q000517:prevention & control*; D058426:Neointima / Q000473:pathology* / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D014680:Veins / Q000473:pathology / Q000601:surgery
chemical_list: C025946:3-methyladenine; D000225:Adenine