LIPOPROTEIN-LIPASE (LPL) AFFECTS LOW-DENSITY-LIPOPROTEIN (LDL) FLUX THROUGH VASCULAR TISSUE - EVIDENCE THAT LPL INCREASES LDL ACCUMULATION IN VASCULAR TISSUE

A cardinal feature of the atherosclerotic lesion is increased low dens ity lipoprotein (LDL) content of the arterial wall. Such increases in vascular wall LDL could result from either increased flux of circulati ng LDL across the arterial endothelial barrier or decreased efflux of LDL that has entered the vascular tissue. A number of studies have foc used on factors that alter permeability of endothelial cell monolayers and intact blood vessels causing increased LDL influx. In contrast, t he current studies were designed to test the hypothesis that lipoprote in lipase (LpL) increases LDL accumulation and decreases LDL efflux fr om vascular tissue. Frog mesenteric venular microvessels were cannulat ed and the rates of fluorescently labeled LDL accumulation (N/t) and e fflux (T-1/2) were measured by quantitative fluorescence microscopy. W hen the vessels were perfused with a solution containing bovine milk L pL (10(-5) g/ml) and human LDL (protein = 0.68 mg/ml), N/t was >15 x g reater than that of control vessels which were perfused with LDL alone . LpL addition did not change albumin permeability, suggesting that in creased N/t was not related to changes in vessel permeability. Increas ed LDL accumulation within the vessel could have resulted from either an increase in LDL influx from the vessel lumen into the vascular tiss ue or a decrease in efflux of LDL. Therefore, LDL efflux from vascular tissue was determined by measuring the rate of decline in fluorescenc e intensity of control and LpL-treated vessels after washout of the ve ssel lumen with a clear, nonfluorescent solution. The half-life of flu orescence 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 indicat ing reduced efflux of LDL in LpL-treated vessels. Heparin prevents int eraction of LpL with proteoglycans on and within the vascular tissue a nd 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 LD L accumulation. These results suggest that the increase in LDL accumul ation requires the interaction of LpL or LpL-LDL complexes with vascul ar tissue proteoglycans. We hypothesize that LpL serves as a molecular bridge between LDL and proteoglycans of in vivo perfused blood vessel s.