Abstract
Introduction: Fatty acids (FAs) have been of interest as biomarkers and as mechanistic signaling modulators of inflammation for the progression of coronary heart disease (CHD). Short chain FAs (SCFA) play a role in two inflammation mediating signaling mechanisms: inhibition of histone deactylase and activation of G-protein-coupled receptors. The omega-3 FAs are important in the generation of resolvins, which are active in the resolution of inflammation. Medium chain FAs (MCFA) play an important role in decreasing cholesterol by inhibiting bile acid reabsorption. In this study we investigated changes of FAs in CHD. Methods: Samples from the Qatar Cardiovascular Biorepository and Qatar Biobank (CHD n=1,001, controls n=2,999) were used for the quantitative analysis of serum FAs by liquid chromatography-mass spectrometry. Data were curated by Metabolon Inc. Standard quality control steps were performed. Logistic regression, adjusting for age, BMI, and sex, was conducted to test association between CHD and FAs. Results: Overall 289 lipid metabolites including 27 long chain FAs (LCFA), 9 MCFA, and one SCFA (caproate) were analyzed. The significant metabolites at P <0.05 were 25 LCFA (20 were higher in CHD), 7 MCFA (4 were higher in CHD), and one SCFA (higher in CHD, P =1.64х10 -87 ). MCFA heptanoate (7:0, P =1.67х10 -26 ), LCFA erucate (22:1n9, P =5.5х10 -8 ) and docosadienoate (20:2n6, P =1.25х10 -5 ) were higher in CHD than controls. Among the FAs that were lower in CHD, there were the long chain omega-3 FAs eicosapentaenoate (EPA, 20:5n3, P =1.6х10 -3 ), docosahexaenoate (DHA, 22:6n3, P =1.45х10 -10 ), and docosapentaenoate (DPA, 22:5n3, P =1.64х10 -11 ), and the MCFA 5-dodecenoate (12:1n7, P =3.5х10 -4 ) and 10-undecenoate (11:1n1, P =3.79х10 -11 ). Conclusions: Our results show that changes in the FAs profile of the CHD patients in this study may mechanistically contribute to the increased prevalence of inflammatory diseases such as CHD in the Middle East.
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