Abstract
Aim: Reverse cholesterol transport (RCT) is one of the main atheroprotective functions of HDL; however no method exists to assess RCT in vivo in humans. We developed a macrophage-specific method using 3H-cholesterol/albumin complexes that has been validated in animal studies. We present the results of a feasibility study in humans. Methods: Thirty subjects received 3H-cholesterol/albumin complexes as i.v. bolus, followed by blood and stool sample collection up to 8 days. Tracer counts were assessed in plasma, non-HDL, HDL and fecal fractions. Data were analyzed using multi-compartmental modeling. Results: Figure 1 shows the tracer kinetics as free cholesterol (FC; panel A) and cholesteryl ester (CE; panel B) specific activity in plasma, HDL and non-HDL. 3H-cholesterol disappeared from plasma rapidly after injection (macrophage uptake of 3H-cholesterol/albumin complexes); nadir was reached by 60 min. Counts present as FC in the HDL fraction increase rapidly and linearly in the first 240 min after nadir (129.9±85.5 cpm/μmols per hour)(3H-cholesterol uptake from macrophages by HDL). Linearity is lost after ∼240 min, as FC is transformed to CE and exchanged with other fractions. In a subset of subjects (n=10), multi-compartmental analysis was used to calculate fractional transfer rates, including macrophage FC to HDL-FC (0.040 ± 0.014 fraction/hour), HDL-FC to HDL-CE (0.238 ± 0.083 fraction/hour), HDL-CE to nonHDL-CE (0.200 ± 0.113 fraction/hour) and fecal excretion (0.032 ± 0.006 fraction/hour). Conclusions: These preliminary data support the feasibility of this approach and suggest that it may be used to measure macrophage RCT in vivo in humans.
Published Version
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