PMID- 30420806
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 9
DP  - 2018
TI  - Sexually Dimorphic Regulation of EET Synthesis and Metabolism: Roles of Estrogen.
PG  - 1222
LID - 10.3389/fphar.2018.01222 [doi]
LID - 1222
AB  - Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid via 
      cytochrome P450 (CYP)/epoxygenase and are hydrolyzed by soluble epoxide hydrolase 
      (sEH). Circulating and tissue levels of EETs are controlled by CYP (EET 
      synthesis) and sEH (EET degradation). Therefore, both increases in CYP activity 
      and decreases in sEH expression potentiate EET bioavailability, responses that 
      prevail in the female sex as a function of estrogen. This mini review, based on 
      subtitles listed, briefly summarizes studies focusing specifically on (1) 
      female-specific potentiation of CYP/epoxygenase activity to compensate for the 
      endothelial dysfunction; and (2) estrogen-dependent downregulation of sEH 
      expression, which yields divergent actions in both systemic and pulmonary 
      circulation, respectively. Estrogen-Potentiating EET Synthesis in Response to 
      Endothelial Dysfunction: This section summarizes the current understanding 
      regarding the roles of estrogen in facilitating EET synthesis in response to 
      endothelial dysfunction. In this regard, estrogen recruitment of EET-driven 
      signaling serves as a back-up mechanism, which compensates for NO deficiency to 
      preserve endothelium-dependent vasodilator responses and maintain normal blood 
      pressure. Estrogen-Dependent Downregulation of Ephx2/sEH Expression: This section 
      focuses on molecular mechanisms responsible for the female-specific 
      downregulation of sEH expression. Roles of EETs in Systemic Circulation, as a 
      Function of Estrogen-Dependent Downregulation of sEH: This section summarizes 
      studies conducted on animals that are either deficient in the Ephx2 gene (sEH-KO) 
      or have been treated with sEH inhibitors (sEHIs), and exhibit EET-mediated 
      cardiovascular protections in the cerebral, coronary, skeletal, and splanchnic 
      circulations. In particular, the estrogen-inherent silencing of the Ephx2 gene 
      duplicates the action of sEH deficiency, yielding comparable adaptations in 
      attenuated myogenic vasoconstriction, enhanced shear stress-induced vasodilation, 
      and improved cardiac contractility among female WT mice, male sEH-KO and 
      sEHI-treated mice. Roles of Estrogen-Driven EET Production in Pulmonary 
      Circulation: This section reviews epidemiological and clinical studies that 
      provide the correlation between the polymorphism, or mutation of gene(s) 
      involving estrogen metabolism and female predisposition to pulmonary 
      hypertension, and specifically addresses an intrinsic causation between the 
      estrogen-dependent downregulation of Ephx2 gene/sEH expression and 
      female-susceptibility of being pulmonary hypertensive, a topic that has never 
      been explored before. Additionally, the issue of the "estrogen paradox" in the 
      incidence and prognosis of pulmonary hypertension is discussed.
FAU - Huang, An
AU  - Huang A
AD  - Department of Physiology, New York Medical College, Valhalla, NY, United States.
FAU - Sun, Dong
AU  - Sun D
AD  - Department of Physiology, New York Medical College, Valhalla, NY, United States.
LA  - eng
GR  - R01 HL070653/HL/NHLBI NIH HHS/United States
GR  - R01 HL129797/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20181029
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC6215857
OTO - NOTNLM
OT  - epoxyeicosatrienoic acids
OT  - estrogen
OT  - pulmonary hypertension
OT  - sex
OT  - soluble epoxide hydrolase
EDAT- 2018/11/14 06:00
MHDA- 2018/11/14 06:01
PMCR- 2018/10/29
CRDT- 2018/11/14 06:00
PHST- 2018/09/04 00:00 [received]
PHST- 2018/10/08 00:00 [accepted]
PHST- 2018/11/14 06:00 [entrez]
PHST- 2018/11/14 06:00 [pubmed]
PHST- 2018/11/14 06:01 [medline]
PHST- 2018/10/29 00:00 [pmc-release]
AID - 10.3389/fphar.2018.01222 [doi]
PST - epublish
SO  - Front Pharmacol. 2018 Oct 29;9:1222. doi: 10.3389/fphar.2018.01222. eCollection 
      2018.