PMID- 31441407
OWN - NLM
STAT- MEDLINE
DCOM- 20191017
LR  - 20191017
IS  - 2095-4352 (Print)
VI  - 31
IP  - 7
DP  - 2019 Jul
TI  - [Effect of unfractionated heparin on high mobility group box 1-mediated 
      expression of vascular endothelial cadherin].
PG  - 842-846
LID - 10.3760/cma.j.issn.2095-4352.2019.07.009 [doi]
AB  - OBJECTIVE: To observe the damage of high mobility group box 1 (HMGB1) on human 
      umbilical vein endothelial cell (HUVEC) barrier permeability and the protective 
      effect of unfractionated heparin (UFH), and to explore the down-regulated 
      protection effect mechanism of UFH on HMGB1-mediated vascular endothelial 
      cadherin (VE-cadherin) expression. METHODS: The trypsin-digested HUVEC were 
      subcultured in culture flasks. When the cells were grown to 80%, they were 
      randomly divided into four groups: phosphate buffer (PBS) control group (200 muL 
      PBS), recombinant human high mobility group box 1 (rhHMGB1) treatment group (100 
      mug/L rhHMGB1), UFH control group (10 kU/L UFH), and UFH pretreatment group (10 
      kU/L UFH+100 mug/L rhHMGB1). The cells in each group were challenged with 
      different reagent for 24 hours, and the activity of endothelial cells was 
      determined by methyl thiazolyl tetrazolium (MTT) colorimetric assay. The 
      permeability of endothelial cells was measured by Transwell method, and the 
      expression and distribution of VE-cadherin was observed by immunofluorescence. 
      The protein expressions of VE-cadherin and phosphorylated p38 mitogen-activated 
      protein kinase (p-p38MAPK) were determined by Western Blot. RESULTS: After 
      treatment with 100 mug/L rhHMGB1 for 24 hours, the activity of endothelial cells 
      was not significantly different from that of the PBS control group (A value: 
      0.230+/-0.004 vs. 0.255+/-0.006, P > 0.05), but the permeability was significantly 
      increased (glucan FD40 fluorescence intensity: 11.05+/-0.12 vs. 6.34+/-0.39, P < 
      0.05). Compared with PBS control group, the fluorescence microscopy showed that 
      the VE-cadherin membrane localization was reduced, the distribution was loose, 
      and there were obvious fissures between cells in rhHMGB1 treatment group, and 
      quantitative analysis showed the protein expression of VE-cadherin was decreased 
      significantly (VE-cadherin/beta-actin: 0.16+/-0.04 vs. 0.31+/-0.03, P < 0.05), and the 
      expression of p-p38MAPK protein was significantly increased (p-p38MAPK/beta-actin: 
      0.79+/-0.03 vs. 0.26+/-0.05, P < 0.05). UFH pretreatment could protect HMGB1-mediated 
      endothelial cell injury, cell permeability was significantly reduced (glucan FD40 
      fluorescence intensity: 9.11+/-0.23 vs. 11.05+/-0.12), fluorescence expression of 
      VE-cadherin was enhanced, membrane localization was significantly increased, 
      quantitative analysis showed that VE-cadherin protein expression was 
      significantly up-regulated (VE-cadherin/beta-actin: 0.24+/-0.02 vs. 0.16+/-0.04), and 
      p38MAPK phosphorylation level was significantly decreased (p-p38MAPK/beta-actin: 
      0.54+/-0.05 vs. 0.79+/-0.03), the difference was statistically significant as 
      compared with rhHMGB1 treatment group (all P < 0.05). There was no significant 
      difference in all parameters between PBS control group and UFH control group. 
      CONCLUSIONS: UFH can protect the endothelial cell barrier from the HMGB1 by 
      regulating the expression and distribution of VE-cadherin. The mechanism may be 
      related to the inhibition of p38MAPK phosphorylation by UFH.
FAU - Wang, Ziang
AU  - Wang Z
AD  - Department of Intensive Care Unit, the First Hospital of China Medical 
      University, Shenyang 110001, Liaoning, China.
FAU - Meng, Yulan
AU  - Meng Y
AD  - Department of Intensive Care Unit, Tacheng Hospital of China Medical University, 
      Tacheng 834700, Xinjiang Uygur Autonomous Region, China. Corresponding author: 
      Luan Zhenggang, Email: luanzhenggang@sina.com.
FAU - Luan, Zhenggang
AU  - Luan Z
AD  - Department of Intensive Care Unit, the First Hospital of China Medical 
      University, Shenyang 110001, Liaoning, China.
LA  - chi
PT  - Journal Article
PL  - China
TA  - Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
JT  - Zhonghua wei zhong bing ji jiu yi xue
JID - 101604552
RN  - 0 (Antigens, CD)
RN  - 0 (Cadherins)
RN  - 0 (Fibrinolytic Agents)
RN  - 0 (HMGB1 Protein)
RN  - 0 (cadherin 5)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Antigens, CD/metabolism
MH  - Cadherins/*metabolism
MH  - Capillary Permeability
MH  - Cells, Cultured
MH  - Endothelial Cells
MH  - Fibrinolytic Agents/*therapeutic use
MH  - HMGB1 Protein/*metabolism
MH  - Heparin/*therapeutic use
MH  - Humans
EDAT- 2019/08/24 06:00
MHDA- 2019/10/18 06:00
CRDT- 2019/08/24 06:00
PHST- 2019/08/24 06:00 [entrez]
PHST- 2019/08/24 06:00 [pubmed]
PHST- 2019/10/18 06:00 [medline]
AID - 10.3760/cma.j.issn.2095-4352.2019.07.009 [doi]
PST - ppublish
SO  - Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2019 Jul;31(7):842-846. doi: 
      10.3760/cma.j.issn.2095-4352.2019.07.009.