Apolipoprotein E and Lipoprotein Lipase Increase Triglyceride-Rich Particle Binding but Decrease Particle Penetration in Arterial Wall

OBJECTIVE: Liver-derived apolipoprotein E (apoE) decreases atherosclerosis without altering the circulating concentrations of plasma lipoproteins. We evaluated the effects of apoE and lipoprotein lipase (LpL) on the interactions of triglyceride-rich particles (TGRPs) in the arterial wall. METHODS AND RESULTS: Quantitative fluorescence microscopy was used to study the interactions of TGRPs (25- to 35-nm diameter) in the arterial wall. Carotid arteries were harvested from rats, placed in a perfusion chamber, and perfused with fluorescently labeled TGRPs. In the absence of apoE or LpL, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine-TGRP (100 microg neutral lipid/mL) was poorly retained in the arterial wall. The addition of either apoE (10 microg/mL) or LpL (10 microg/mL) increased TGRP accumulation 220% and 100%, respectively. This effect was attenuated by heparin (10.0 IU/mL). Histological analyses of cross sections from these vessels demonstrate that in the absence of apoE or LpL, there is deep penetration of lipid into the arterial wall. With the addition of either apoE or LpL, arterial wall penetration of TGRP is blocked. CONCLUSIONS: These results demonstrate that although apoE and LpL increase arterial wall accumulation of TGRPs, these proteins also reduce the penetration of TGRPs into the arterial wall. We postulate that this may represent a novel antiatherogenic property of apoE and LpL.