A cardinal feature of the atherosclerotic lesion is increased low density lipoprotein (LDL) content of the arterial wall. Such increases in vascular wall LDL could result from either increased flux of circulating LDL across the arterial endothelial barrier or decreased efflux of LDL that has entered the vascular tissue. A number of studies have focused on factors that alter permeability of endothelial cell monolayers and intact blood vessels causing increased LDL influx. In contrast, the current studies were designed to test the hypothesis that lipoprotein lipase (LpL) increases LDL accumulation and decreases LDL efflux from vascular tissue. Frog mesenteric venular microvessels were cannulated and the rates of fluorescently labeled LDL accumulation (N/t) and efflux (T( 1/2 )) were measured by quantitative fluorescence microscopy. When the vessels were perfused with a solution containing bovine milk LpL (10-5 g/ml) and human LDL (protein = 0.68 mg/ml), N/t was >15 x greater than that of control vessels which were perfused with LDL alone. LpL addition did not change albumin permeability, suggesting that increased N/t was not related to changes in vessel permeability. Increased LDL accumulation within the vessel could have resulted from either an increase in LDL influx from the vessel lumen into the vascular tissue or a decrease in efflux of LDL. Therefore, LDL efflux from vascular tissue was determined by measuring the rate of decline in fluorescence intensity of control and LpL-treated vessels after washout of the vessel lumen with a clear, nonfluorescent solution. The half-life of fluorescence decay after LDL perfusions (T( 1/2 )) was 4.2 ± 1.6 (SD) sec and 53.3 ± 15.5 sec after LpL (10-5 g/ml) was added to LDL indicating reduced efflux of LDL in LpL-treated vessels. Heparin prevents interaction of LpL with proteoglycans on and within the vascular tissue and in low concentration does not interfere with the enzymatic actions of LpL. Addition of heparin to solutions containing LDL and LpL almost completely eliminated the LpL- mediated increase in vascular tissue LDL accumulation. These results suggest that the increase in LDL accumulation requires the interaction of LpL or LpL- LDL complexes with vascular tissue proteoglycans. We hypothesize that LpL serves as a molecular bridge between LDL and proteoglycans of in vivo perfused blood vessels.
|Original language||English (US)|
|Number of pages||9|
|Journal||Journal of Lipid Research|
|State||Published - 1994|
- blood vessels
- fluorescence microscopy
ASJC Scopus subject areas