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 de termined by the balance between the inflow and outflow of plasma lipoprotei ns in the arterial wall. Whereas the rate of inflow may be measured directl y, the rate of outflow has most often been calculated indirectly from lipop rotein uptake by using the 2-compartment model. One objection against such calculations is that lipoprotein binding is not being considered. In the pr esent study 2 different protocols were used to obtain a direct measure of t he outflow of lipoproteins from atherosclerotic rabbit aortas. Thus, 3 rabb its with experimental atherosclerosis were given I-125-LDL intravenously an d 3 were given [C-14]cholesterol perorally. Twenty-four hours later the aor tas were removed and the outflow of label was monitored during in vitro per fusion. Despite the different protocols, our results were consistent and in dicated that fractional loss relative to whole tissue was approximate to 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 m uch as 2/3 to 3/4 Of the tracer that had entered the arterial wall was effe ctively trapped, the remainder equilibrated at a faster rate (0.06 pool/h). In conclusion, it seems that tissue binding constitutes a prominent and po ssibly underrated mechanism of lipoprotein deposition, at least in the athe rosclerotic rabbit aorta. Furthermore, this means that current estimates of lipoprotein exchange parameters based on the 2-compartment model (eg, frac tional loss) may rest on invalid assumptions and should be regarded with ca ution.