LIPOPROTEIN-LIPASE INCREASES LIPOPROTEIN BINDING TO THE ARTERY WALL AND INCREASES ENDOTHELIAL LAYER PERMEABILITY BY FORMATION OF LIPOLYSIS PRODUCTS

Mechanisms responsible for the accumulation of low-density lipoprotein (LDL) were investigated in a new model, the perfused hamster aorta. T o do this, we developed a method to study LDL flux in real time in ind ividually perfused arteries; each artery served as its own control. Us ing quantitative fluorescence microscopy, the rates of LDL accumulatio n and efflux were separately determined. Perfusion of arteries with bu ffer plus lipoprotein lipase (LpL) increased LDL accumulation 5-fold ( 0.1+/-0.03 mV/min [control] versus 0.5+/-0.05 mV/min [LpL]) by increas ing LDL retention in the artery wall. This effect was blocked by hepar in and monoclonal antibodies directed against the amino-terminal regio n of apolipoprotein B (ape B). This suggests that specific regions of apo B are involved in LDL accumulation within arteries. Also, the effe ct of hydrolysis of triglyceride-rich lipoproteins on endothelial barr ier function was studied. We compared endothelial layer permeability u sing a water-soluble reference molecule, fluorescently labeled dextran . When LpL was added to hypertriglyceridemic plasma? dextran accumulat ion within the artery wall increased >4-fold (0.024+/-0.01 mV/min [con trol] versus 0.098+/-0.05 mV/min [LpL]). Under the same conditions, Lp L increased LDL accumulation approximate to 3-fold (0.016+/-0.003 mV/m in [control] versus 0.047+/-0.013 mV/min [LpL]). Rapid efflux of LDL f rom the artery wall indicated that increased endothelial layer permeab ility was the primary mechanism during periods of increased lipolysis. Our data demonstrate two LpL-mediated effects that may increase the a mount of LDL in the artery wall. These findings may pertain to the obs erved relationship between increased postprandial lipemia and atherosc lerosis.