Abstract 13049: Serum FABP5 Concentration, a Novel Determinant of Cholesterol Efflux From Macrophages, is a Potential Biomarker for Residual Risk of Atherosclerosis

Abstract

Introduction: Cholesterol efflux capacity (CEC) from macrophages, represents the reverse cholesterol transport pathway, is inversely associated with risk for atherosclerotic cardiovascular disease. Fatty acid-binding protein 4 (FABP4) and 5 (FABP5) are expressed in both adipocytes and macrophages and play significant roles in the development of insulin resistance and atherosclerosis. FABP4 and FABP5 have been shown to be secreted from cells, and the circulating levels are associated with insulin resistance and atherosclerosis. Hypothesis: Serum levels of FABP4 and FABP5 are independently associated with CEC. Methods: A total of 250 subjects who were not on medication were recruited from subjects of the Tanno-Sobetsu Study, a study with a population-based cohort design. Concentrations of FABP4 and FABP5 were measured using commercially available enzyme-linked immunosorbent assay kits. CEC was measured using apolipoprotein B-depleted serum and J774.1 cells, a murine macrophage cell line. Results: CEC was positively correlated with HDL cholesterol and was negatively correlated with concentrations of high-sensitivity C-reactive protein (hsCRP) and FABP5 (r = -0.180, P = 0.041) but not with FABP4 level. Multiple regression analysis demonstrated that FABP5 level was an independent predictor of CEC after adjustment of age, gender and levels of HDL cholesterol and hsCRP. In 129 out of 250 subjects who underwent carotid ultrasonography, mean intima-media thickness was negatively correlated with CEC (r = -0.248, P = 0.005) and was positively correlated with concentrations of FABP4 (r = 0.178, P = 0.043) and FABP5 (r = 0.194, P = 0.028). Conclusions: In contrast to FABP4, FABP5 is independently associated with both carotid atherosclerosis and decreased CEC, suggesting that FABP5 level is a novel regulatory factor of CEC and a potential biomarker for residual risk of atherosclerosis in relation to cholesterol efflux from macrophages.