The Effects Of Soluble Epoxide Hydrolase Inhibitors On The Expression Of Fatty Acid Synthase In Peripheral Blood Mononuclear Cell Of ACS Pateints

Objectives:We will observe the effect of soluble epoxide hydrolase inhibitor (sEHi) on the expression of FASN mRNA and protein in peripheral blood mononuclear cell (PBMC) of patients with acute coronary syndrome (ACS). This research aim to discusse the influence of sEHi in regulating fatty acid metabolism and resisting inflammatory reaction, which would help to rich the knowledge of sEHi's anti-arteriosclerosis mechanism, and looking for new therapeutic targets and prevention interventions for arteriosclerosis(AS).Methods:We chose the acute coronary syndrome (ACS) patients from XiangYa the second affiliated hospital during December 2010 to February 2011 as ACS group (35 cases) and healthy normal human as normal control group (30 cases). Basic biochemical indicators were measured in 24 hours after the patients was admitted, including serum total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting blood sugar (FBS), myocardial enzyme (CK-Mb, cTNT) and hight sensitive c-reactive protein (hs-CRP) concentration. Meanwhile, we separat the peripheral blood mononuclear cell (PBMC) from blood of patients, then t-AUCB in various concentrations (0,1,10,50,100μmol/L) were added for co-incubation for 24 hours. We extract total mRNA and protein from cells after 24h cultivation. The expression level of FASN, IL-6 mRNA and protein were compared between ACS and normal group, control group and intervention groups. The amounts of total protein of FASN, IL-6 mRNA expression in cells were detected by realtime-PCR, and protein level were examined via western blot.Results:1. Compared with normal control group, the serum concentration of hs-CRP, expression level of FASN, IL-6 mRNA and protein were significantly increased in the ACS group (P<0.05). Moreover, FASN, IL-6 respectively had positive association 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 Oμmol/L), t-AUCB had inhibited FASN, IL-6 mRNA expression in PBMC from the ACS group under different concentrations (10,50,100μmol/L) (P<0.05).3. FASN, IL-6 protein expression level in PBMC of ACS patients reduced after t-AUCB intervention, and the decrease became significant when the concentration reach 50umol/L and 100μmol/L, to be compared with the control group (t-AUCB 0μmol/L) (P<0.05).Conclusions:1. Compared with the normal control group, The FASN expression in PBMC was increased obviously in ACS group, and had a positive association with serum concentration of hs-CRP, suggesting that the FASN expression level in PBMC of ACS patients is closely related with inflammation, which might be an indicator of inflammatory state in the body.2. t-AUCB could inhibit FASN, IL-6 mRNA and protein expression in PBMC of ACS group, thus inhibiting fatty acid metabolism and monocyte differentiation which related to FASN, and inflammatory reaction right in the AS plaque. All these may be the mechanism for sEHi to perform a protect function on atherogensis.