The effects of lipoprotein hydrolysis by lipoprotein lipase on human macrophages
Lipoprotein lipase (LPL) is a member of an extracellular lipase family that hydrolyzes triglycerides within circulating lipoproteins. LPL is expressed in several tissues, including macrophages. In macrophages, the products of lipoprotein hydrolysis, provided by LPL, has been considered to be detrimental in atherosclerosis. However, the mechanisms behind this process are poorly understood. We hypothesized that the products of lipoprotein hydrolysis may promote atherogenesis by modulating lipid synthesis, metabolism and transport. To test our hypothesis, we have performed quantitative real time-PCR analyses on THP-1 macrophages which were incubated with the hydrolysis products of human total lipoproteins by LPL. We quantified the expression level of cholesterol transporters and transcriptional regulators, together with genes involved in lipid synthesis and metabolism. Our analyses suggest that the products of lipoprotein hydrolysis may promote atherogenesis by inhibiting the cholesterol efflux. We also quantified the level of individual molecular species for each class of lipid using electrospray ionization mass spectrometry (ESI-MS). With the ESI-MS data, our laboratory is currently working on revealing candidate lipids that may be responsible for the influencing our observed changes in gene expression. Our work will ultimately provide further insight into the potential roles of LPL in modulating atherogenesis.