Abstract 13029: Mechanism of the Low Cholesterol Esterification Rate in Human Interstitial Fluid (Peripheral Lymph)
Glomset’s observation (J Lipid Res 1968; 9: 155) that the esterification of cholesterol (UC) by lecithin: cholesterol acyltransferase (LCAT) enhances the transfer of UC from erythrocytes to high-density lipoproteins (HDLs) in plasma suggested that LCAT drives reverse cholesterol transport (RCT). However, later findings that HDLs in afferent (prenodal) peripheral lymph (L) are discoidal and enriched in UC showed that UC efflux from most cells exceeds its extracellular esterification rate. To explore the underlying mechanism, we compared plasma (P) and L from 20 healthy men. During incubation at 37°C, endogenous cholesterol esterification rate (ECER) in L was 4.3±1.9% of that in P (mean±SD; P≤0.01). LCAT activity assayed with [3H]UC-labeled proteoliposomes was 10.4±4.1% of that in P; concentrations of LCAT, apo A1 and UC were 12.1±4.1%, 21.5±6.2% and 8.7±4.0%, respectively (all P≤0.01). Addition of recombinant human LCAT to L, P, LCAT-deficient P, or heat-inactivated P (HIP) increased LCAT activity equally. Addition of apo A1, albumin, or very low-density lipoprotein (VLDL, d≤1.006 g/mL plasma fraction) to L had no effect on ECER. Addition of apo A1/lecithin discs (final conc, 0.66 mg apo A1/mL) increased ECER in L by 5.9±2.0 fold (P≤0.01). Mixtures of equal vols of (a) L and buffer, (b) L and P, and (c) L and HIP gave the following ECERs: [a] 36±6, [b] 1508±67, and [c] 392±133 pmol UC esterified/6h (n=5 subjects; b and c both P≤0.01 vs a).
Conclusions: (1) L contains sufficient LCAT and apo A1 to esterify UC; (2) L does not contain an LCAT inhibitor; (3) Endogenous HDLs in L are poor substrates for LCAT. By preventing the accumulation of CE in HDLs that would otherwise occur in the absence of VLDL, this may be to facilitate the passage of the particles through the interstices of the extracellular matrix of peripheral tissues.
- © 2013 by American Heart Association, Inc.