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 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 (T1/2) 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 > 15x 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Rutledge
J C
JC
Departments of Medicine, University of California, Davis 95616.
Goldberg
I J
IJ
D000418:Albumins / Q000378:metabolism; D000818:Animals; D003911:Dextrans / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology; D008071:Lipoprotein Lipase / Q000502:physiology*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008833:Microcirculation / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D010477:Perfusion; D011894:Rana pipiens
D000418:Albumins; D003911:Dextrans; D008077:Lipoproteins, LDL; D006493:Heparin; D008071:Lipoprotein Lipase