FABP4

Fatty acid binding protein 4 (FABP4), also known as adipocyte P2 and A FABP (adipocyte FABP), is a FABP family member that is expressed in adipocytes and monocyte derived foam cells. It is a lipid transport protein that binds long chain fatty acid and retinoic acid. Human and mouse FABP4 share a 91% amino acid sequence homology. FABP4 plays an important role in maintaining glucose and lipid homeostasis and has been primarily regarded as an adipocyte- and macrophage-specific protein. However recent studies suggest that it may be more widely expressed. A strong FABP4 expression was found in endothelial cells (ECs) of capillaries and small veins in several mouse and human tissues, including the heart and kidney. FABP4 was also detected in the ECs of mature human placental vessels and infantile hemangiomas, the most common tumor of infancy and ECs. In most of these cases, FABP4 was detected in both the nucleus and cytoplasm. FABP4 mRNA and protein levels were significantly induced in cultured ECs by VEGF-A and bFGF treatment. The effect of VEGF-A on FABP4 expression was inhibited by chemical inhibition or short-hairpin (sh) RNA-mediated knockdown of VEGFR-2 (KDR), whereas the VEGFR1 agonists, PlGF-1 and PlGF-2, had no effect on FABP4 expression. Knockdown of FABP4 in ECs significantly reduced proliferation both under baseline conditions and in response to VEGF and bFGF. Thus, FABP4 emerged as a novel target of the VEGF/VEGFR-2 pathway and a positive regulator of cell proliferation in ECs.