[Effects of soluble epoxide hydrolase inhibitors on the expression of fatty acid synthase in peripheral blood mononuclear cell of patients and inflammatory response with acute coronary syndrome]

Zhonghua Yi Xue Za Zhi. 2012 Jan 10;92(2):86-90.
[Article in Chinese]

Abstract

Objective: To explore the effects of soluble epoxide hydrolase inhibitor (sEHi) on the expressions of fatty acid synthase (FASN) mRNA and protein in peripheral blood mononuclear cell (PBMCs) of patients with acute coronary syndrome (ACS) and to discuss the influences of sEHi in the regulated expression of FASN and inflammatory reaction.

Methods: The hospitalized ACS patients were selected as the ACS group (n = 35) while the healthy normal subjects as the control group (n = 30). The levels of lipoproteins, fasting blood glucose, myocardial enzyme and hs-CRP (high-sensitive C-reactive protein) were measured within 24 hours after admission. Meanwhile the PBMCs were separated and cultured and then t-AUCB was added in various concentrations (0, 1, 10, 50, 100 µmol/L). The cellular expressions of FASN, IL-6 mRNA and protein were detected by real-time PCR (polymerase chain reaction) and Western blot respectively.

Results: (1) The serum concentration of hs-CRP reached (5.6 ± 4.1) mg/L in the ACS group. And it was obviously higher than (1.3 ± 0.9) mg/L in the control group (P < 0.05). Compared with the control group, the expression levels of FASN, IL-6 mRNA and protein significantly increased in the ACS group (the relative expression amount of FASN mRNA: 1 vs 1.709 ± 0.272, FASN protein: 0.407 ± 0.065 vs 1.298 ± 0.087; relative expression amount of IL-6 mRNA: 1 vs 2.302 ± 0.200, IL-6 protein: 0.715 ± 0.058 vs 1.146 ± 0.083, P < 0.05). Moreover, the levels of FASN and IL-6 mRNA had positive correlations with the serum concentration of hs-CRP (r = 0.714, P < 0.01; r = 0.685, P < 0.01). (2) Compared with the control group (t-AUCB 0 µmol/L), 10, 50, 100 µmol/L t-AUCB had inhibited the expressions quantity of FASN, IL-6 mRNA and protein in PBMCs from the ACS group (P < 0.05). The relative expressions of FASN mRNA in t-AUCB 0, 10, 50, 100 µmol/L group were 1, 0.813 ± 0.038, 0.564 ± 0.100, 0.293 ± 0.043 respectively. The relative expressions of FASN protein in t-AUCB 0, 10, 50 and 100 µmol/L group were 0.957 ± 0.280, 0.935 ± 0.275, 0.855 ± 0.253, 0.685 ± 0.206 respectively.

Conclusion: The inflammatory level increases obviously in the ACS group. And the expression level of FASN in PBMCs is closely correlated with the inflammatory level in the ACS patients; t-AUCB may prevent the ruptures of atherosclerotic lesions by regulating FASN and inhibiting inflammatory reactions in ACS patients.

Publication types

  • English Abstract
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acute Coronary Syndrome / blood*
  • Acute Coronary Syndrome / pathology*
  • Aged
  • Benzoates / pharmacology*
  • Case-Control Studies
  • Epoxide Hydrolases / antagonists & inhibitors*
  • Fatty Acid Synthase, Type I / metabolism*
  • Female
  • Humans
  • Inflammation*
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • Urea / analogs & derivatives*
  • Urea / pharmacology

Substances

  • 4-(4-(3-adamantan-1-ylureido)cyclohexyloxy)benzoic acid
  • Benzoates
  • Urea
  • FASN protein, human
  • Fatty Acid Synthase, Type I
  • Epoxide Hydrolases