Abstract
BackgroundResearches 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.MethodsHospitalized 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).ConclusionssEH 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.
Highlights
Researches have shown that soluble epoxide hydrolase inhibitors can protect against the development of atherosclerosis
Basic clinical characteristics of the study subjects There was no statistical significance between the acute coronary syndrome (ACS) group and the control group in terms of gender, age, number of people who smoke, body mass index (BMI), blood pressure, fasting blood sugar (FBS), hemoglobin (Hb), serum creatinine(Cr), TG, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), LDL-C
Expressions of fatty acid synthase (FAS), IL-6 mRNA and protein in peripheral blood mononuclear cells (PBMCs) and their relationships with high-sensitive C-reactive protein (hs-CRP) As shown in Figure 1, compared with the control group, the mRNA and protein expression levels of FAS and IL6 were significantly increased in the ACS group
Summary
Researches have shown that soluble epoxide hydrolase inhibitors (sEHi) can protect against the development of atherosclerosis. Emerging evidences have implicated the association between fatty acid synthase (FAS) and acute coronary syndrome (ACS). Numerous studies have shown that the concentrations of saturated fatty acid (SFA) in plaques and the thickness of the fibrous cap are associated with the formation of disrupted plaques [5]. Evidence suggests that FAS is the key enzyme that regulates differentiation of the monocyte into the macrophage, and the inhibition of FAS limits phagocytosis by macrophages [9]. Macrophages release lytic enzymes that degrade the fibrous cap, resulting in plaque instability and rupture [10]. The inhibition of FAS could decrease ACS by reducing the number of macrophages present in the plaque and preventing phagocytosis by macrophages
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