Lipoprotein lipase (LPL) is an extracellular lipase that primarily hydrolyses
triglycerides within circulating lipoproteins. Macrophage LPL contributes to
atherogenesis, but the mechanisms behind it are poorly understood. I hypothesized that
the free fatty acid (FFA) component of the products of lipoprotein hydrolysis generated
by LPL promotes atherogenesis by inhibiting the cholesterol efflux ability by
macrophages. To test my hypothesis, THP-1 macrophages were incubated overnight with
lipoprotein hydrolysis products generated by LPL. Results showed that the hydrolysis
products negatively modulated the transcripts encoding nuclear receptors, cholesterol
transporters, and enzymes involved in FFA synthesis. A mixture of only purified FFA that
matches those liberated by LPL yielded comparable results to those for lipoprotein
hydrolysis products. Furthermore, the FFA mixture significantly attenuated
apolipoprotein A-I-mediated cholesterol efflux. Overall, these data show that lipoprotein
hydrolysis products generated by LPL may promote atherogenesis by inhibiting
cholesterol efflux, which partially explains the pro-atherogenic role of macrophage LPL
