PMID- 29462373
OWN - NLM
STAT- MEDLINE
DCOM- 20190925
LR  - 20190925
IS  - 1524-4040 (Electronic)
IS  - 0148-396X (Linking)
VI  - 83
IP  - 6
DP  - 2018 Dec 1
TI  - The Role of Matrix Metalloproteinase-3 in the Doxycycline Attenuation of 
      Intracranial Venous Hypertension-Induced Angiogenesis.
PG  - 1317-1327
LID - 10.1093/neuros/nyx633 [doi]
AB  - BACKGROUND: The molecular mechanism of brain arteriovenous malformation (BAVM) is 
      largely unknown. Intracranial venous hypertension (VH) may enhance focal 
      angiogenesis and promote BAVM development and progression. A rat VH model 
      effectively simulates the hemodynamic microenvironment of this disease. 
      OBJECTIVE: To explore the effect of doxycycline in VH-related angiogenesis, as 
      well as the role of matrix metalloproteinase-3 (MMP-3) and other molecular 
      factors. METHODS: A rat VH model was generated by common carotid artery and 
      distal external jugular vein anastomosis. Microvessel density (MVD) in the 
      perisinus area and expression of MMP-3/2/9, VEGF, TIMP-1, TGF-beta, and HIF-1alpha were 
      examined, with and without daily doxycycline treatment for 4 wk. The effects of 
      doxycycline were verified in Vitro using human brain microvascular endothelial 
      cells (HBMECs). MMP-3 overexpression or knockdown in HBMECs was used to confirm 
      the role of MMP-3 in cell functions. RESULTS: MVD in the perisinus cortex was 
      greatly increased after VH. Doxycycline decreased MVD, suppressed MMP-3 
      overexpression, and reduced VEGF, TGF-beta, and TIMP-1 levels compared with the 
      controls (P < .05). In Vitro, doxycycline decreased HBMEC migration, tube 
      formation, and the mRNA, protein, and enzymatic activity levels of MMP-3. MMP-3 
      overexpression in HBMECs promoted migration, while knockdown of MMP-3 
      significantly attenuated proliferation, migration, and tube formation (P < .05). 
      CONCLUSION: Our findings indicate that MMP-3 plays an important role in 
      VH-related angiogenesis and the promotion of vascular remodeling. Suppression of 
      MMP-3 overexpression by doxycycline may provide a potential strategy for 
      inhibiting BAVM development.
FAU - Zou, Xiang
AU  - Zou X
AD  - Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan 
      University, Shanghai, China.
FAU - Wu, Zehan
AU  - Wu Z
AD  - Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan 
      University, Shanghai, China.
FAU - Huang, Jun
AU  - Huang J
AD  - Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.
AD  - The Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China.
FAU - Liu, Peixi
AU  - Liu P
AD  - Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan 
      University, Shanghai, China.
FAU - Qin, Xuanfeng
AU  - Qin X
AD  - Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan 
      University, Shanghai, China.
FAU - Chen, Liang
AU  - Chen L
AD  - Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan 
      University, Shanghai, China.
FAU - Zhu, Wei
AU  - Zhu W
AD  - Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan 
      University, Shanghai, China.
FAU - Zhao, Yao
AU  - Zhao Y
AD  - Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan 
      University, Shanghai, China.
FAU - Li, Peiliang
AU  - Li P
AD  - Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan 
      University, Shanghai, China.
FAU - Song, Jianping
AU  - Song J
AD  - Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan 
      University, Shanghai, China.
FAU - Yang, Guo-Yuan
AU  - Yang GY
AD  - Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.
FAU - Mao, Ying
AU  - Mao Y
AD  - Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan 
      University, Shanghai, China.
AD  - State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences 
      and Institutes of Brain Science, Fudan University, Shanghai, China.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Neurosurgery
JT  - Neurosurgery
JID - 7802914
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - N12000U13O (Doxycycline)
SB  - IM
MH  - Animals
MH  - Doxycycline/*pharmacology
MH  - Humans
MH  - Intracranial Arteriovenous Malformations/metabolism
MH  - Intracranial Hypertension/*metabolism
MH  - Male
MH  - Matrix Metalloproteinase 3/*metabolism
MH  - Neovascularization, Pathologic/*metabolism
MH  - Rats
MH  - Vascular Remodeling/*drug effects/physiology
EDAT- 2018/02/21 06:00
MHDA- 2019/09/26 06:00
CRDT- 2018/02/21 06:00
PHST- 2017/09/09 00:00 [received]
PHST- 2017/12/22 00:00 [accepted]
PHST- 2018/02/21 06:00 [pubmed]
PHST- 2019/09/26 06:00 [medline]
PHST- 2018/02/21 06:00 [entrez]
AID - 4865224 [pii]
AID - 10.1093/neuros/nyx633 [doi]
PST - ppublish
SO  - Neurosurgery. 2018 Dec 1;83(6):1317-1327. doi: 10.1093/neuros/nyx633.