Lipoprotein lipase (LPL) is an extracellular lipase that preferentially hydrolyses triglycerides in triglyceride-rich lipoproteins within the circulation. LPL expression in macrophages contributes to atherosclerosis. In addition, the hydrolysis products liberated from lipoprotein lipids by LPL causes lipid accumulation and impairs cholesterol efflux ability in macrophages. However, the effects of LPL hydrolysis products in modulating the transcript profiles within macrophages and their roles in foam cell formation are not completely understood. We performed microarray analyses on THP-1 macrophages incubated with LPL hydrolysis products to identify differentially expressed genes. Overall design: Human LPL was recombinantly expressed in HEK-293T cells. Heparinized media from cells expressing LPL or from control cells were used to hydrolyse total lipoproteins that were isolated from normolipidemic subjects. THP-1 macrophages were incubated with 0.68 mM (by unesterified fatty acid content) of LPL hydrolysis products, or non-hydrolysis products (of 0.03 mM by unesterified fatty acid content) for 18 hours (n=3). Total RNA was isolated from treated samples and it was used for human gene arrays.