title: Evaluation of hepatic vascular endothelial injury during liver storage by molecular detection and targeted contrast-enhanced ultrasound imaging.
abstract: We hypothesized that lack of the high-energy phosphates during liver storage may potentially cause persistent injury to the vascular endothelium. Biopsies were obtained from livers obtained from beating heart human donors, stored either in the standard storage solution, that is, University of Wisconsin solution (UWS) or Celsior, and examined for various markers related to progressive endothelial injury. The expression of P2Y1 receptor, the major signal transduction machinery for adenosine triphosphate/adenosine diphosphate, decreased in hepatic vascular endothelial cells over time. Despite unaltered endothelial nitric oxide synthase (eNOS) levels, serine1177-phosphorylated eNOS, the active form of eNOS, progressively decreased with time. The production of nitric oxide enzyme decreased with time when liver tissues were examined in vitro. This also coincided with decreased interaction of eNOS with actin nucleating proteins like myristoylated alanine-rich C kinase substrate and Rac1, which plays a role in modulating the cytoskeleton and helps position eNOS in a favorable cytosolic position for active enzymatic activity. Conversely, the interaction of eNOS with caveolin1 was significantly increased 6 H after ex vivo storage. Finally, we demonstrated by targeted contrast-enhanced ultrasound that membrane-bound vascular cell adhesion molecule-1 in the hepatic vascular endothelial cell increased after 6 H of ex vivo storage. Overall, the results of this study provide evidence of a progressive hepatic vascular endothelial injury during the ex vivo storage. This may be a causative factor for ischemic cholangiopathy and delayed graft function post liver transplantation. © 2015 IUBMB Life, 68(1):51-57, 2015.
authors.affiliation: Department of Ultrasound, Chinese PLA General Hospital, Beijing, China.|Department of Ultrasound, North China University of Science and Technology Affiliated Hospital, Tangshan, Hebei, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Xie
authors.affiliation: Department of Ultrasound, North China University of Science and Technology Affiliated Hospital, Tangshan, Hebei, China.
authors.forename: Shu-Hua
authors.initials: SH
authors.lastname: Zhang
authors.affiliation: Department of Ultrasound, Chinese PLA General Hospital, Beijing, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Ultrasound, Chinese PLA General Hospital, Beijing, China.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Wang
authors.affiliation: Department of Ultrasound, Chinese PLA General Hospital, Beijing, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Fei
authors.affiliation: Department of Ultrasound, Chinese PLA General Hospital, Beijing, China.
authors.forename: Zi-Yu
authors.initials: ZY
authors.lastname: Jiao
authors.affiliation: Department of Ultrasound, Chinese PLA General Hospital, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Ultrasound, Chinese PLA General Hospital, Beijing, China.
authors.forename: Yu-Kun
authors.initials: YK
authors.lastname: Luo
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D008099:Liver; D016031:Liver Transplantation; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009926:Organ Preservation; D058472:Receptors, Purinergic P2Y1 / Q000378:metabolism; D014021:Tissue Preservation; D014463:Ultrasonography; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D058472:Receptors, Purinergic P2Y1; D019010:Vascular Cell Adhesion Molecule-1; D000255:Adenosine Triphosphate; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III
keywords: biliary; ischemic cholangiopathy; liver transplantation; targeted contrast-enhanced ultrasound; vascular endothelial injury