title: Effects of soluble epoxide hydrolase inhibitor on the expression of fatty acid synthase in peripheral blood mononuclear cell in patients with acute coronary syndrome.
abstract: BACKGROUND
  Researches have shown that soluble epoxide hydrolase inhibitors (sEHi) can protect against the development of atherosclerosis. Simultaneously, emerging evidences have implicated the association between fatty acid synthase (FAS) and acute coronary syndrome (ACS). We tested the hypothesis that sEHi could reduce the occurrence of ACS by regulating FAS.
  
  
  METHODS
  Hospitalized ACS patients were selected as the ACS group (n = 65) while healthy normal subjects as the control group (n = 65). The blood levels of lipoproteins, fasting glucose, myocardial enzyme and high-sensitivity C-reactive protein (hs-CRP) were measured within 24 hours after admission. The peripheral blood mononuclear cells (PBMCs) were isolated and cultured. Trans-4-[4-(3-Adamantan-1-ylureido)cyclohexyloxy] benzoic acid (t-AUCB), a kind of sEHi, was then added to cells in various concentrations (0, 10, 50, 100 μmol/L). The expression of FAS, interleukin-6 (IL-6) mRNA and protein was detected by real-time PCR or Western blot, respectively.
  
  
  RESULTS
  (1) Compared with the control group, the serum concentration of hs-CRP in the ACS group was increased (P<0.05). The expression of FAS, IL-6 mRNA and protein were significantly increased in PBMCs from the ACS group (all P<0.05). Moreover, the levels of FAS and IL-6 mRNA were positively correlated with the serum concentration of hs-CRP (r = 0.685, P<0.01; r = 0.715, P<0.01) respectively. (2) The expression of FAS, IL-6 mRNA and protein in PBMCs from the ACS group were dose-dependently inhibited by sEHi (all P<0.05).
  
  
  CONCLUSIONS
  sEH inhibition regulated FAS and inhibited inflammation in cultured PBMCs from ACS patients, a mechanism that might prevent rupture of atherosclerotic lesions and protect against development of ACS.
authors.affiliation: Department of Cardiology & Internal Medicine, Second Xiangya Hospital, Central South University, 139 Middle Ren min Road, Changsha, 410011, PR China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhao
authors.forename: Jian-qing
authors.initials: JQ
authors.lastname: Du
authors.forename: Dan-yan
authors.initials: DY
authors.lastname: Xu
authors.forename: Shui-ping
authors.initials: SP
authors.lastname: Zhao
mesh_terms: D054058:Acute Coronary Syndrome / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D001565:Benzoates / Q000494:pharmacology*; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D054890:Fatty Acid Synthase, Type I / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012995:Solubility; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C524106:4-(4-(3-adamantan-1-ylureido)cyclohexyloxy)benzoic acid; D001565:Benzoates; D004791:Enzyme Inhibitors; C508600:IL6 protein, human; D015850:Interleukin-6; D012333:RNA, Messenger; D014508:Urea; D002097:C-Reactive Protein; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I; D004851:Epoxide Hydrolases