PMID- 29232926
OWN - NLM
STAT- MEDLINE
DCOM- 20180717
LR  - 20200525
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 18
IP  - 12
DP  - 2017 Dec 11
TI  - Differential Effects of sEH Inhibitors on the Proliferation and Migration of 
      Vascular Smooth Muscle Cells.
LID - 10.3390/ijms18122683 [doi]
LID - 2683
AB  - Epoxyeicosatrienoic acid (EET) is a cardioprotective metabolite of arachidonic 
      acid. It is known that soluble epoxide hydrolase (sEH) is involved in the 
      metabolic degradation of EET. The abnormal proliferation and migration of 
      vascular smooth muscle cells (VSMCs) play important roles in the pathogenesis of 
      atherosclerosis and restenosis. Thus, the present study investigated the effects 
      of the sEH inhibitor 
      12-(((tricyclo(3.3.1.13,7)dec-1-ylamino)carbonyl)amino)-dodecanoic acid (AUDA) on 
      platelet-derived growth factor (PDGF)-induced proliferation and migration in rat 
      VSMCs. AUDA significantly inhibited PDGF-induced rat VSMC proliferation, which 
      coincided with Pin1 suppression and heme oxygenase-1 (HO-1) upregulation. 
      However, exogenous 8,9-EET, 11,12-EET, and 14,15-EET treatments did not alter 
      Pin1 or HO-1 levels and had little effect on the proliferation of rat VSMCs. On 
      the other hand, AUDA enhanced the PDGF-stimulated cell migration of rat VSMCs. 
      Furthermore, AUDA-induced activation of cyclooxygenase-2 (COX-2) and subsequent 
      thromboxane A2 (TXA(2)) production were required for the enhanced migration. 
      Additionally, EETs increased COX-2 expression but inhibited the migration of rat 
      VSMCs. In conclusion, the present study showed that AUDA exerted differential 
      effects on the proliferation and migration of PDGF-stimulated rat VSMCs and that 
      these results may not depend on EET stabilization.
FAU - Kim, Hyo Seon
AU  - Kim HS
AD  - College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul 
      National University, Seoul 08826, Korea. hyoseonkim@snu.ac.kr.
FAU - Kim, Sang Kyum
AU  - Kim SK
AD  - College of Pharmacy, Chungnam National University, Daejeon 34134, Korea. 
      sangkim@cnu.ac.kr.
FAU - Kang, Keon Wook
AU  - Kang KW
AD  - College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul 
      National University, Seoul 08826, Korea. kwkang@snu.ac.kr.
LA  - eng
PT  - Journal Article
DEP - 20171211
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Epoxy Compounds)
RN  - 0 (Lauric Acids)
RN  - 0 (PDZD2 protein, rat)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/metabolism
MH  - Animals
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Enzyme Inhibitors/*pharmacology
MH  - Epoxide Hydrolases/*antagonists & inhibitors
MH  - Epoxy Compounds/*metabolism
MH  - Gene Expression Regulation/drug effects
MH  - Heme Oxygenase-1/metabolism
MH  - Lauric Acids/*pharmacology
MH  - Muscle, Smooth, Vascular/*cytology/drug effects/metabolism
MH  - Myocytes, Smooth Muscle/cytology/drug effects/metabolism
MH  - Rats
PMC - PMC5751285
OTO - NOTNLM
OT  - cyclooxygenase-2
OT  - epoxyeicosatrienoic acid
OT  - soluble epoxide hydrolase
OT  - vascular smooth muscle cell
COIS- The authors declare no conflict of interest. The founding sponsors had no role in 
      the design of the study; in the collection, analyses, or interpretation of data; 
      in the writing of the manuscript; or in the decision to publish the results.
EDAT- 2017/12/14 06:00
MHDA- 2018/07/18 06:00
PMCR- 2017/12/01
CRDT- 2017/12/14 06:00
PHST- 2017/10/24 00:00 [received]
PHST- 2017/11/30 00:00 [revised]
PHST- 2017/12/08 00:00 [accepted]
PHST- 2017/12/14 06:00 [entrez]
PHST- 2017/12/14 06:00 [pubmed]
PHST- 2018/07/18 06:00 [medline]
PHST- 2017/12/01 00:00 [pmc-release]
AID - ijms18122683 [pii]
AID - ijms-18-02683 [pii]
AID - 10.3390/ijms18122683 [doi]
PST - epublish
SO  - Int J Mol Sci. 2017 Dec 11;18(12):2683. doi: 10.3390/ijms18122683.