Direct assessment of lipoprotein outflow from in vivo-labeled arterial tissue as determined in an in vitro perfusion system.
The rate of cholesterol deposition during the atherosclerotic process is determined by the balance between the inflow and outflow of plasma lipoproteins in the arterial wall. Whereas the rate of inflow may be measured directly, the rate of outflow has most often been calculated indirectly from lipoprotein uptake by using the 2-compartment model. One objection against such calculations is that lipoprotein binding is not being considered. In the present study 2 different protocols were used to obtain a direct measure of the outflow of lipoproteins from atherosclerotic rabbit aortas. Thus, 3 rabbits with experimental atherosclerosis were given 125I-LDL intravenously and 3 were given [14C]cholesterol perorally. Twenty-four hours later the aortas were removed and the outflow of label was monitored during in vitro perfusion. Despite the different protocols, our results were consistent and indicated that fractional loss relative to whole tissue was approximately 0.01 pool/h, which is 1 order of magnitude lower than current estimates based on the 2-compartment model (0.04 to 0.4 pool/h). Furthermore, whereas as much as 2/3 to 3/4 of the tracer that had entered the arterial wall was effectively trapped, the remainder equilibrated at a faster rate (0.06 pool/h). In conclusion, it seems that tissue binding constitutes a prominent and possibly underrated mechanism of lipoprotein deposition, at least in the atherosclerotic rabbit aorta. Furthermore, this means that current estimates of lipoprotein exchange parameters based on the 2-compartment model (eg, fractional loss) may rest on invalid assumptions and should be regarded with caution.
Björnheden
T
T
Wallenberg Laboratory for Cardiovascular Research, University of Göteborg, Sweden. tom.bjornheden@wlab.wall.gu.se tom.bjornheden@wlab.wall.gu.se
Bondjers
G
G
Wiklund
O
O
D000818:Animals; D001158:Arteries / Q000378:metabolism*; D001161:Arteriosclerosis / Q000378:metabolism; D002250:Carbon Radioisotopes; D002784:Cholesterol / Q000378:metabolism; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D011817:Rabbits
D002250:Carbon Radioisotopes; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL; D002784:Cholesterol