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Correspondence to:
Allan D. Sniderman
In comparison to very low density lipoprotein (VLDL), chylomicrons are cleared quickly from plasma. However, small changes in fasting plasma VLDL concentration substantially delay postprandial chylomicron triglyceride clearance. We hypothesized that differential binding to lipoprotein lipase (LPL), the first step in the lipolytic pathway, might explain these otherwise paradoxical relationships. Competition binding assays of different lipoproteins were performed in a solid phase assay with purified bovine LPL at 4°C. The results showed that chylomicrons, VLDL, and low density lipoprotein (LDL) were able to inhibit specific binding of 125I-labeled VLDL to the same extent (85.1% ± 13.1, 100% ± 6.8, 90.7% ± 23.2% inhibition, P = NS), but with markedly different efficiencies. The rank order of inhibition (Ki) was chylomicrons (0.27 ± 0.02 nM apoB) > VLDL (12.6 ± 3.11 nM apoB) > LDL (34.8 ± 11.1 nM apoB). By contrast, neither triglyceride (TG) liposomes, high density lipoprotein (HDL), nor LDL from patients with familial hypercholesterolemia were efficient at displacing the specific binding of 125I-labeled VLDL to LPL (30%, 39%, and no displacement, respectively). Importantly, smaller hydrolyzed chylomicrons had less affinity than the larger chylomicrons (Ki = 2.34 ± 0.85 nM vs. 0.27 ± 0.02 nM apoB respectively, P < 0.01). This was also true for hydrolyzed VLDL, although to a lesser extent. Chylomicrons from patients with LPL deficiency and VLDL from hypertriglyceridemic subjects were also studied.
Taken together, our results indicate an inverse linear relationship between chylomicron size and Ki whereas none was present for VLDL. We hypothesize that the differences in binding affinity demonstrated in vitro when considered with the differences in particle number observed in vivo may largely explain the paradoxes we set out to study.Xiang, S-Q., K. Cianflone, D. Kalant, and A. D. Sniderman. Differential binding of triglyceride-rich lipoproteins to lipoprotein lipase. J. Lipid Res. 1999. 40: 1655;1662.
Supplementary key words:
binding, lipoprotein lipase, lipoproteins, triglyceride clearance
Copyright © 1999 by Lipid Research, Inc.
Original Article
Differential binding of triglyceride-rich lipoproteins to lipoprotein lipase
Shi-Qin Xianga,
Katherine Cianflonea,
David Kalanta, and
Allan D. Snidermana
a Mike Rosenbloom Laboratory for Cardiovascular Research, McGill University Health Center, Montreal, Quebec H3A 1A1, Canada
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