PMID- 28545777
OWN - NLM
STAT- MEDLINE
DCOM- 20180530
LR  - 20180530
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 811
DP  - 2017 Sep 15
TI  - Inhibitory effects of doxycycline on the onset and progression of abdominal 
      aortic aneurysm and its related mechanisms.
PG  - 101-109
LID - S0014-2999(17)30372-2 [pii]
LID - 10.1016/j.ejphar.2017.05.041 [doi]
AB  - The objective of this study was to investigate whether doxycycline (DOX) given at 
      different doses and via different administration routes had protective or 
      therapeutic effects on abdominal aortic aneurysm (AAA) induced by elastase in 
      mice. Moreover, the anti-AAA mechanism of DOX was studied in TNF-alpha-stimulated 
      vascular smooth muscle cell (VSMC) in vitro. For in vivo study, either daily 
      administration of 30mg/kg of DOX by gavage or intraperitoneal injection of 
      15mg/kg DOX every other day for 14 days significantly prevented the development 
      of AAA at its early stage. Further study showed that intraperitoneal injection of 
      15mg/kg DOX every other day for 7 times in total could also cure the established 
      AAA. In vitro study showed that treating VSMCs with TNF-alpha together with DOX 
      remarkably inhibited the expressions and activities of MMPs (MMP-2 and MMP-9), 
      significantly suppressed the activation of protein kinase B (AKT) signaling 
      pathway and mitogen-activated protein kinases (MAPKs) signal proteins, including 
      extracellular signal-regulated kinase (ERK), c-Jun amino-terminal kinases (JNK) 
      and p38, and downregulated mRNA levels of interleukin-6 (IL-6) and monocyte 
      chemotactic protein 1 (MCP-1), and significantly upregulated mRNA levels of 
      transforming growth factor beta (TGF-beta), heme oxygenase 1 (HO-1) and superoxide 
      dismutase 1 (SOD-1), indicating that DOX inhibits activities of MMPs through 
      reducing oxidative stress, suppressing MAPKs and AKT signaling pathways and 
      ameliorating inflammation in VSMCs, and therefore, exerts preventive as well as 
      therapeutic effects on AAA.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Yu, Maomao
AU  - Yu M
AD  - Institute of Cardiovascular Sciences, Peking University Health Science Center, 
      Peking University, Beijing 100191, China; Key Laboratory of Molecular 
      Cardiovascular Sciences, Ministry of Education, Beijing 100191, China; Beijing 
      Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Beijing 
      100191, China.
FAU - Chen, Cong
AU  - Chen C
AD  - Institute of Cardiovascular Sciences, Peking University Health Science Center, 
      Peking University, Beijing 100191, China; Key Laboratory of Molecular 
      Cardiovascular Sciences, Ministry of Education, Beijing 100191, China; Beijing 
      Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Beijing 
      100191, China.
FAU - Cao, Yini
AU  - Cao Y
AD  - Institute of Cardiovascular Sciences, Peking University Health Science Center, 
      Peking University, Beijing 100191, China; Key Laboratory of Molecular 
      Cardiovascular Sciences, Ministry of Education, Beijing 100191, China; Beijing 
      Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Beijing 
      100191, China.
FAU - Qi, Rong
AU  - Qi R
AD  - Institute of Cardiovascular Sciences, Peking University Health Science Center, 
      Peking University, Beijing 100191, China; Key Laboratory of Molecular 
      Cardiovascular Sciences, Ministry of Education, Beijing 100191, China; Beijing 
      Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Beijing 
      100191, China. Electronic address: ronaqi@bjmu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20170522
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Biomarkers)
RN  - 0 (Cytokines)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - N12000U13O (Doxycycline)
SB  - IM
MH  - Animals
MH  - Aorta/drug effects/metabolism/pathology/physiopathology
MH  - Aortic Aneurysm, Abdominal/genetics/metabolism/pathology/*prevention & control
MH  - Biomarkers/metabolism
MH  - Cytokines/genetics
MH  - *Disease Progression
MH  - Dose-Response Relationship, Drug
MH  - Doxycycline/*pharmacology
MH  - Gene Expression Regulation, Enzymologic/drug effects
MH  - MAP Kinase Signaling System/drug effects
MH  - Male
MH  - Matrix Metalloproteinase 2/metabolism
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Mice
MH  - Muscle, Smooth, Vascular/drug effects/pathology
MH  - Oxidative Stress/drug effects
MH  - Phosphorylation/drug effects
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - RNA, Messenger/genetics/metabolism
OTO - NOTNLM
OT  - Abdominal aortic aneurysm
OT  - Doxycycline
OT  - Elastase
OT  - Inflammation
OT  - MMPs
OT  - VSMC
EDAT- 2017/05/27 06:00
MHDA- 2018/05/31 06:00
CRDT- 2017/05/27 06:00
PHST- 2017/02/26 00:00 [received]
PHST- 2017/03/22 00:00 [revised]
PHST- 2017/05/22 00:00 [accepted]
PHST- 2017/05/27 06:00 [pubmed]
PHST- 2018/05/31 06:00 [medline]
PHST- 2017/05/27 06:00 [entrez]
AID - S0014-2999(17)30372-2 [pii]
AID - 10.1016/j.ejphar.2017.05.041 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2017 Sep 15;811:101-109. doi: 10.1016/j.ejphar.2017.05.041. Epub 
      2017 May 22.