Lipoprotein Lipase Increases Lipoprotein Binding to the Artery Wall and Increases Endothelial Layer Permeability by Formation of Lipolysis Products

Abstract

Mechanisms responsible for the accumulation of low-density lipoprotein (LDL) were investigated in a new model, the perfused hamster aorta. To do this, we developed a method to study LDL flux in real time in individually perfused arteries; each artery served as its own control. Using quantitative fluorescence microscopy, the rates of LDL accumulation and efflux were separately determined. Perfusion of arteries with buffer 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 increasing LDL retention in the artery wall. This effect was blocked by heparin and monoclonal antibodies directed against the amino-terminal region of apolipoprotein B (apo B). This suggests that specific regions of apo B are involved in LDL accumulation within arteries. Also, the effect of hydrolysis of triglyceride-rich lipoproteins on endothelial barrier function was studied. We compared endothelial layer permeability using a water-soluble reference molecule, fluorescently labeled dextran. When LpL was added to hypertriglyceridemic plasma, dextran accumulation within the artery wall increased > 4-fold (0.024 +/- 0.01 mV/min [control] versus 0.098 +/- 0.05 mV/min [LpL]). Under the same conditions, LpL increased LDL accumulation approximately 3-fold (0.016 +/- 0.003 mV/min [control] versus 0.047 +/- 0.013 mV/min [LpL]). Rapid efflux of LDL from the artery wall indicated that increased endothelial layer permeability was the primary mechanism during periods of increased lipolysis. Our data demonstrate two LpL-mediated effects that may increase the amount of LDL in the artery wall. These findings may pertain to the observed relationship between increased postprandial lipemia and atherosclerosis.

Effect of a moderate weight loss on adipose tissue lipoprotein lipase activity and expression: existence of sexual variation and regional differences

“…These results could be partly explained by the role of LPL in the retention of LDL in the subendothelial matrix. 50 …”

Modified LDL–Mediated Increases in Endothelial Layer Permeability Are Attenuated With 17β-Estradiol

“…6,30 Rats were anesthetized by intraperitoneal injection of sodium pentobarbital (35 mg/kg). After the rat was anesthetized, a midline incision was made in the neck, and both carotid arteries were dissected free from connective tissue.…”

“…Therefore, molecule accumulation in the artery wall was determined photometrically (in millivolts) and was a measure of the number of fluorescent molecules that remained on the lumen surface or in the artery wall. 6 The rate of molecule accumulation is If accumulation divided by perfusion time. Using this approach, we were able to measure If accumulation multiple times ( Figure 2).…”

“…32 The rates of DiI-N-LDL, DiI-MM-LDL, and DiI-OX-LDL efflux were determined, as we have described previously. 6 In summary, the rate of decay of fluorescence intensity was determined after the fluorescently labeled LDL solution was washed from the vessel lumen. The decay in fluorescence then represents the efflux of LDL back into the artery lumen.…”

“…[1][2][3] Sites of relative increase in LDL permeability have been identified in normal arteries 4 and can be induced by injury to the endothelium. [5][6][7][8][9] Alternatively, others have reported increased binding and decreased efflux of LDL from the vascular wall, even under conditions where LDL influx was not affected. 10,11 Therefore, LDL accumulation in the artery wall potentially occurs by several mechanisms, perhaps depending on the stage of atheroma formation.…”