Abstract
Cholesterol efflux capacity (CEC) from macrophages, the first step in the reverse cholesterol transport pathway, is inversely associated with residual risk for atherosclerotic cardiovascular disease. Fatty acid-binding protein 4 (FABP4) and FABP5 are expressed in both adipocytes and macrophages and play significant roles in the development of insulin resistance and atherosclerosis. Both FABP4 and FABP5 are secreted from cells, and their circulating levels are associated with insulin resistance and atherosclerosis. We investigated the association between CEC and levels of FABP4 and FABP5 in 250 subjects without any medications. CEC was positively correlated with HDL cholesterol level and negatively correlated with concentrations of high-sensitivity C-reactive protein (hsCRP) and FABP5, but not FABP4. Multiple regression analysis demonstrated that FABP5 concentration was an independent predictor of CEC after adjustment of age, gender and levels of HDL cholesterol and hsCRP. In 129 of the 250 subjects who underwent carotid ultrasonography, mean intima-media thickness was negatively correlated with CEC and was positively correlated with concentrations of FABP4 and FABP5. In conclusion, in contrast to FABP4, circulating FABP5 is associated with decreased CEC and carotid atherosclerosis, suggesting that FABP5 level is a regulatory factor of CEC and a potential biomarker for residual risk of atherosclerosis.
Highlights
high-density lipoprotein (HDL) cholesterol level[7,8,9,10], providing supportive evidence for the significance of HDL functionality over simple measurement of HDL cholesterol level
The present study showed for the first time that serum fatty acid-binding protein 5 (FABP5) concentration was an independent negative predictor of cholesterol efflux capacity (CEC) in connection with mean intima-media thickness (IMT) in a general population who had not taken any medication, suggesting a link between circulating FABP5 and carotid atherosclerosis via reduction of cholesterol efflux in macrophages
Therapies targeting quality of HDL rather than quantity of HDL might be effective for prevention of atherosclerotic cardiovascular disease and prevention of recurrence, though it is necessary to determine whether CEC is associated with progression of atherosclerosis in subjects with no medication
Summary
HDL cholesterol level[7,8,9,10], providing supportive evidence for the significance of HDL functionality over simple measurement of HDL cholesterol level. Previous studies using FABP4- and FABP5-deficient mice demonstrated that both FABP4 and FABP5 play significant roles in the development of insulin resistance, diabetes mellitus and atherosclerosis[14,15,16,17,18,19]. Elevated circulating FABP4 level is associated with obesity, insulin resistance, type 2 diabetes mellitus, dyslipidemia, hypertension, renal dysfunction, cardiac dysfunction, atherosclerosis and cardiovascular events[23,24,25,26,27,28,29,30,31,32,33,34]. Circulating FABP4 has recently been reported to act as an adipokine for the development of insulin resistance[21], and neutralization of FABP4 with an antibody to FABP4 could be a feasible approach for the treatment of diabetes mellitus[35]. We investigated the cross-sectional association between CEC, circulating levels of FABP4 and FABP5 and intima-media thickness (IMT), a marker of carotid atherosclerosis assessed by using carotid ultrasonography, in a general population who had not regularly taken any medications
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