PMID- 27579889
OWN - NLM
STAT- MEDLINE
DCOM- 20170821
LR  - 20190212
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 8
DP  - 2016
TI  - beta2-Glycoprotein I Inhibits Vascular Endothelial Growth Factor-Induced 
      Angiogenesis by Suppressing the Phosphorylation of Extracellular Signal-Regulated 
      Kinase 1/2, Akt, and Endothelial Nitric Oxide Synthase.
PG  - e0161950
LID - 10.1371/journal.pone.0161950 [doi]
LID - e0161950
AB  - Angiogenesis is the process of new blood vessel formation, and it plays a key 
      role in various physiological and pathological conditions. The beta2-glycoprotein I 
      (beta2-GPI) is a plasma glycoprotein with multiple biological functions, some of 
      which remain to be elucidated. This study aimed to identify the contribution of 
      2-GPI on the angiogenesis induced by vascular endothelial growth factor (VEGF), a 
      pro-angiogenic factor that may regulate endothelial remodeling, and its 
      underlying mechanism. Our results revealed that beta2-GPI dose-dependently decreased 
      the VEGF-induced increase in endothelial cell proliferation, using the 
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and the 
      bromodeoxyuridine (BrdU) incorporation assays. Furthermore, incubation with both 
      beta2-GPI and deglycosylated beta2-GPI inhibited the VEGF-induced tube formation. Our 
      results suggest that the carbohydrate residues of beta2-GPI do not participate in 
      the function of anti-angiogenesis. Using in vivo Matrigel plug and angioreactor 
      assays, we show that beta2-GPI remarkably inhibited the VEGF-induced angiogenesis at 
      a physiological concentration. Moreover, beta2-GPI inhibited the VEGF-induced 
      phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), Akt, and 
      endothelial nitric oxide synthase (eNOS). In summary, our in vitro and in vivo 
      data reveal for the first time that beta2-GPI inhibits the VEGF-induced angiogenesis 
      and highlights the potential for beta2-GPI in anti-angiogenic therapy.
FAU - Chiu, Wen-Chin
AU  - Chiu WC
AD  - Institute of Biochemistry and Molecular Biology, National Yang-Ming University, 
      Taipei, Taiwan.
AD  - Division of Thoracic Surgery, Department of Surgery, Kaohsiung Medical University 
      Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
FAU - Chiou, Tzeon-Jye
AU  - Chiou TJ
AD  - Division of Transfusion Medicine, Department of Medicine, Taipei Veterans General 
      Hospital and National Yang-Ming University School of Medicine, Taipei, Taiwan.
FAU - Chung, Meng-Ju
AU  - Chung MJ
AD  - Institute of Biochemistry and Molecular Biology, National Yang-Ming University, 
      Taipei, Taiwan.
FAU - Chiang, An-Na
AU  - Chiang AN
AD  - Institute of Biochemistry and Molecular Biology, National Yang-Ming University, 
      Taipei, Taiwan.
LA  - eng
PT  - Journal Article
DEP - 20160831
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (beta 2-Glycoprotein I)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
SB  - IM
MH  - Animals
MH  - Aorta/*cytology/drug effects/metabolism
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Endothelial Cells/cytology/*drug effects/metabolism
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Neovascularization, Pathologic/chemically induced/*metabolism
MH  - Nitric Oxide Synthase Type III/metabolism
MH  - Phosphorylation/drug effects
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction/drug effects
MH  - Vascular Endothelial Growth Factor A/*pharmacology
MH  - beta 2-Glycoprotein I/*pharmacology
PMC - PMC5006999
COIS- The authors have declared that no competing interests exist.
EDAT- 2016/09/01 06:00
MHDA- 2017/08/22 06:00
PMCR- 2016/08/31
CRDT- 2016/09/01 06:00
PHST- 2016/02/23 00:00 [received]
PHST- 2016/08/15 00:00 [accepted]
PHST- 2016/09/01 06:00 [entrez]
PHST- 2016/09/01 06:00 [pubmed]
PHST- 2017/08/22 06:00 [medline]
PHST- 2016/08/31 00:00 [pmc-release]
AID - PONE-D-16-07716 [pii]
AID - 10.1371/journal.pone.0161950 [doi]
PST - epublish
SO  - PLoS One. 2016 Aug 31;11(8):e0161950. doi: 10.1371/journal.pone.0161950. 
      eCollection 2016.