title: Propofol-enhanced autophagy increases motility and angiogenic capacity of cultured human umbilical vascular endothelial cells.
abstract: OBJECTIVE
  Propofol (PPF), an intravenous anesthetic agent, is previously reported to attenuate oxidative stress- and inflammation-induced endothelial cell dysfunction. This study investigated its effect on endothelial cell biology.
  
  
  METHODS
  Cultured human umbilical vein endothelial cells (HUVECs) were treated with PPF and subject to measurements for nitric oxide (NO) production, autophagy flux, signal transduction, migration, and in vitro angiogenesis.
  
  
  RESULTS
  Non-cytotoxic PPF treatment was found to significantly upregulate inducible nitric oxide synthase (NOS2) but downregulate constitutive NOS3 expression. It also potentiated LPS-induced ICAM-1 overexpression and NO overproduction. Mechanistically, the PPF-activated signal transduction in PI3K/Akt, ERK1/2, p38 MAPK, and JNK pathways were involved in the PPF-driven NO overproduction. PPF exhibited a stimulatory effect on autophagy flux by increasing expression of autophagy markers including mTOR, Beclin-1, Atg5, and LC3I/II, as well as a late endosomal indicator, Rab7. However, PPF appeared to antagonize the Rab7 upregulation by LPS. Functionally, PPF enhanced in vitro migratory and angiogenic capacities of HUVECs, but this enhancement was drastically abrogated by the presence of autophagy inhibitors, indicating a pro-angiogenic contribution of PPF-enhanced autophagy in cultured HUVECs.
  
  
  CONCLUSIONS
  Our findings support the notion that PPF enhances motility and angiogenic capacity of cultured HUVECs through an autophagy-involved regulatory mechanism.
authors.affiliation: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, E-Da Hospital, Kaohsiung 824, Taiwan.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Chang
authors.affiliation: Department of Medical Research, E-Da Hospital, Kaohsiung 824, Taiwan.
authors.forename: Po-Han
authors.initials: PH
authors.lastname: Chen
authors.affiliation: Department of Medical Research, E-Da Hospital, Kaohsiung 824, Taiwan.
authors.forename: Shang-Chieh
authors.initials: SC
authors.lastname: Lu
authors.affiliation: Department of Medical Research, E-Da Hospital, Kaohsiung 824, Taiwan.
authors.forename: Ming-Chu
authors.initials: MC
authors.lastname: Hsieh
authors.affiliation: Department of Medical Research, E-Da Hospital, Kaohsiung 824, Taiwan.
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Lin
authors.affiliation: Department of Surgery, E-Da Hospital, Kaohsiung 824, Taiwan.
authors.forename: Hui-Ming
authors.initials: HM
authors.lastname: Lee
authors.affiliation: Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan. Electronic address: jawanb@adm.cgmh.org.tw.
authors.forename: Bruno
authors.initials: B
authors.lastname: Jawan
authors.affiliation: Department of Medical Research, E-Da Hospital, Kaohsiung 824, Taiwan; Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung 831, Taiwan. Electronic address: danyhkao@gmail.com.
authors.forename: Ying-Hsien
authors.initials: YH
authors.lastname: Kao
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009569:Nitric Oxide / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D015742:Propofol / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D015742:Propofol
keywords: Angiogenesis; Autophagosomes; Autophagy flux; Migration; Nitric oxide synthase; Signal transduction