PMID- 28056085
OWN - NLM
STAT- MEDLINE
DCOM- 20170828
LR  - 20191220
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 1
DP  - 2017
TI  - Vascular Endothelial Over-Expression of Human Soluble Epoxide Hydrolase (Tie2-sEH 
      Tr) Attenuates Coronary Reactive Hyperemia in Mice: Role of Oxylipins and 
      omega-Hydroxylases.
PG  - e0169584
LID - 10.1371/journal.pone.0169584 [doi]
LID - e0169584
AB  - Cytochromes P450 metabolize arachidonic acid (AA) into two vasoactive oxylipins 
      with opposing biologic effects: epoxyeicosatrienoic acids (EETs) and 
      omega-(omega)-terminal hydroxyeicosatetraenoic acids (HETEs). EETs have numerous 
      beneficial physiological effects, including vasodilation and protection against 
      ischemia/reperfusion injury, whereas omega-terminal HETEs induce vasoconstriction and 
      vascular dysfunction. We evaluated the effect of these oxylipins on post-ischemic 
      vasodilation known as coronary reactive hyperemia (CRH). CRH prevents the 
      potential harm associated with transient ischemia. The beneficial effects of EETs 
      are reduced after their hydrolysis to dihydroxyeicosatrienoic acids (DHETs) by 
      soluble epoxide hydrolase (sEH). omega-terminal HETEs are formed by omega-hydroxylase 
      family members. The relationship among endothelial over-expression of sEH 
      (Tie2-sEH Tr), the changes in oxylipins it may produce, the pharmacologic 
      inhibition of omega-hydroxylases, activation of PPARgamma, and CRH response to a brief 
      ischemia is not known. We hypothesized that CRH is attenuated in isolated mouse 
      hearts with endothelial sEH over-expression through modulation of oxylipin 
      profiles, whereas both inhibition of omega-hydroxylases and activation of PPARgamma 
      enhance CRH. Compared to WT mice, Tie2-sEH Tr mice had decreased CRH, including 
      repayment volume, repayment duration, and repayment/debt ratio (P < 0.05), 
      whereas inhibition of omega-hydroxylases increased these same CRH parameters in 
      Tie2-sEH Tr mice. Inhibition of sEH with t-AUCB reversed the decreased CRH in 
      Tie2-sEH Tr mice. Endothelial over-expression of sEH significantly changed 
      oxylipin profiles, including decreases in DHETs, mid-chain HETEs, and 
      prostaglandins (P < 0.05). Treatment with rosiglitazone, PPARgamma-agonist, enhanced 
      CRH (P < 0.05) in both Tie2-sEH Tr and wild type (WT) mice. These data 
      demonstrate that endothelial over-expression of sEH (through changing the 
      oxylipin profiles) attenuates CRH, whereas inhibition of omega-hydroxylases and 
      activation of PPARgamma enhance it.
FAU - Hanif, Ahmad
AU  - Hanif A
AD  - Basic Pharmaceutical Sciences, School of Pharmacy, Center for Basic and 
      Translational Stroke Research. West Virginia University, Morgantown, West 
      Virginia, United States of America.
FAU - Edin, Matthew L
AU  - Edin ML
AD  - Division of Intramural Research, NIEHS/NIH, Research Triangle Park, North 
      Carolina, United States of America.
FAU - Zeldin, Darryl C
AU  - Zeldin DC
AD  - Division of Intramural Research, NIEHS/NIH, Research Triangle Park, North 
      Carolina, United States of America.
FAU - Morisseau, Christophe
AU  - Morisseau C
AD  - University of California at Davis, One Shields Avenue, Davis, California, United 
      States of America.
FAU - Falck, John R
AU  - Falck JR
AD  - Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas, 
      United States of America.
FAU - Nayeem, Mohammed A
AU  - Nayeem MA
AUID- ORCID: 0000-0002-7827-4760
AD  - Basic Pharmaceutical Sciences, School of Pharmacy, Center for Basic and 
      Translational Stroke Research. West Virginia University, Morgantown, West 
      Virginia, United States of America.
LA  - eng
GR  - R01 HL114559/HL/NHLBI NIH HHS/United States
GR  - Z01 ES025034/Intramural NIH HHS/United States
PT  - Journal Article
DEP - 20170105
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Hydroxyeicosatetraenoic Acids)
RN  - 0 (Oxylipins)
RN  - 0 (PPAR gamma)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
SB  - IM
MH  - Animals
MH  - Chromatography, Liquid
MH  - Coronary Disease/*enzymology/genetics/*metabolism
MH  - Endothelium, Vascular/metabolism/*physiopathology
MH  - Epoxide Hydrolases/genetics/*metabolism
MH  - Humans
MH  - Hydroxyeicosatetraenoic Acids/metabolism
MH  - Hyperemia/genetics/*metabolism/*physiopathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Oxylipins/*metabolism
MH  - PPAR gamma/agonists/metabolism
MH  - Tandem Mass Spectrometry
PMC - PMC5215949
COIS- The authors have declared that no competing interests exist.
EDAT- 2017/01/06 06:00
MHDA- 2017/08/29 06:00
PMCR- 2017/01/05
CRDT- 2017/01/06 06:00
PHST- 2016/10/13 00:00 [received]
PHST- 2016/12/19 00:00 [accepted]
PHST- 2017/01/06 06:00 [entrez]
PHST- 2017/01/06 06:00 [pubmed]
PHST- 2017/08/29 06:00 [medline]
PHST- 2017/01/05 00:00 [pmc-release]
AID - PONE-D-16-40923 [pii]
AID - 10.1371/journal.pone.0169584 [doi]
PST - epublish
SO  - PLoS One. 2017 Jan 5;12(1):e0169584. doi: 10.1371/journal.pone.0169584. 
      eCollection 2017.