title: A Switch in the Dynamics of Intra-Platelet VEGF-A from Cancer to the Later Phase of Liver Regeneration after Partial Hepatectomy in Humans.
abstract: BACKGROUND
  Liver regeneration (LR) involves an early inductive phase characterized by the proliferation of hepatocytes, and a delayed angiogenic phase distinguished by the expansion of non-parenchymal compartment. The interest in understanding the mechanism of LR has lately shifted from the proliferation and growth of parenchymal cells to vascular remodeling during LR. Angiogenesis accompanied by LR exerts a pivotal role to accomplish the process. Vascular endothelial growth factor (VEGF) has been elucidated as the most dynamic regulator of angiogenesis. From this perspective, platelet derived/Intra-platelet (IP) VEGF-A should be associated with LR.
  
  
  METHODS
  Thirty-seven patients diagnosed with hepatocellular carcinoma and undergoing partial hepatectomy (PH) were enrolled in the study. Serum and IP VEGF-A was monitored preoperatively and at four weeks of PH. Liver volumetry was determined on computer models derived from computed tomography (CT) scan.
  
  
  RESULTS
  Serum and IP VEGF-A was significantly elevated at four weeks of PH. Preoperative IP VEGF-A was higher in patients with advanced cancer and vascular invasion. Postoperative IP VEGF-A was higher after major liver resection. There was a statistically significant correlation between postoperative IP VEGF-A and the future remnant liver volume. Moreover, the soluble vascular endothelial growth factor receptor-1 (sVEGFR1) was distinctly down-regulated suggesting a fine-tuned angiogenesis at the later phase of LR.
  
  
  CONCLUSIONS
  IP VEGF-A is overexpressed during later phase of LR suggesting its implications in inducing angiogenesis during LR.
authors.affiliation: Cardiovascular and Gastroenterological Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Bibek
authors.initials: B
authors.lastname: Aryal
authors.affiliation: Department of Laboratory and Vascular Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Cardiovascular and Gastroenterological Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kadono
authors.affiliation: Department of Surgery, Kirishima Medical Center, Kirishima, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Furoi
authors.affiliation: Department of Surgery, Kagoshima Medical Center, National Hospital Organization, Kagoshima, Japan.
authors.forename: Teruo
authors.initials: T
authors.lastname: Komokata
authors.affiliation: Department of Surgery, Kirishima Medical Center, Kirishima, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Inoue
authors.affiliation: Department of Radiology, Kirishima Medical Center, Kirishima, Japan.
authors.forename: Shunichiro
authors.initials: S
authors.lastname: Ikeda
authors.affiliation: Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Fukukura
authors.affiliation: Department of Clinical Laboratory, Kagoshima University Medical and Dental Hospital, Kagoshima, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Laboratory and Vascular Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Munekazu
authors.initials: M
authors.lastname: Yamakuchi
authors.affiliation: Department of Laboratory and Vascular Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Teruto
authors.initials: T
authors.lastname: Hashiguchi
authors.affiliation: Cardiovascular and Gastroenterological Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Imoto
mesh_terms: D000368:Aged; D001792:Blood Platelets / Q000737:chemistry / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000503:physiopathology / Q000601:surgery*; D016207:Cytokines / Q000097:blood / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006498:Hepatectomy; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000502:physiology; D008113:Liver Neoplasms / Q000503:physiopathology / Q000601:surgery*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000502:physiology*
chemical_list: D016207:Cytokines; D015850:Interleukin-6; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A