Figure 2

Putative mechanism of the development of atherosclerosis by secreted FABP4 and FABP5. The expression of FABP5 is about one-hundredth of that of FABP4 in adipose tissue, and the amount of FABP4 in adipocytes is about 10,000-fold larger than that in macrophages (ref. 11). The stoichiometry of FABP4 and that of FABP5 in macrophages are almost identical (ref. 15). Both FABP4 and FABP5 are secreted from adipocytes and macrophages (refs 21,22,23 and 39). Direct effects of exogenous FABP4 in various types of cells have been demonstrated. Treatment with recombinant FABP4 inhibited activation of endothelial nitric oxide synthase in vascular endothelial cells, increased proliferation/migration of vascular smooth muscle cells (VSMC) and induced inflammatory responses in macrophages, vascular endothelial cells and VSMC (ref. 23), leading to the development of atherosclerosis. In the present study, the level of FABP5, but not that of FABP4, was an independent negative predictor of cholesterol efflux capacity (CEC) as an HDL function, indicating that circulating FABP5 contributes to the development of atherosclerosis via reduction of CEC in macrophages. The mechanism of direct association between CEC and FABP5 level needs to be addressed in experimental models.