Remodeling of HDL remnants generated by scavenger receptor class B type I

Abstract

Scavenger receptor class B type I (SR-BI) mediates the selective transfer of cholesteryl ester from HDL to cells. We previously established that SR-BI overexpressed in livers of apolipoprotein A-I-deficient mice processes exogenous human HDL 2 to incrementally smaller HDL particles. When mixed with normal mouse plasma either in vivo or ex vivo, SR-BI-generated HDL "remnants" rapidly remodel to form HDL-sized lipoproteins. In this study, we analyzed HDLs throughout the process of HDL remnant formation and investigated the mechanism of conversion to larger particles. Upon interacting with SR-BI, ␣ -migrating HDL 2 is initially converted to a pre ␣ -migrating particle that is ultimately processed to a smaller ␣ -migrating HDL remnant. SR-BI does not appear to generate pre ␤ -1 HDL particles. When incubated with isolated lipoprotein fractions, HDL remnants are converted to lipoprotein particles corresponding in size to the particle incubated with the HDL remnant. HDL remnant conversion is not altered in phospholipid transfer protein (PLTP)-deficient mouse plasma or by the addition of purified PLTP. Although LCAT-deficient plasma promoted only partial conversion, this deficiency was attributable to the nature of HDL particles in LCAT ؊ / ؊ mice rather than to a requirement for LCAT in the remodeling process. We conclude that HDL remnants, generated by SR-BI, are converted to larger particles by rapidly reassociating with existing HDL particles in an enzyme-independent manner. -Webb, N. R., M. C. de Beer, B. F. Asztalos, N. Whitaker, D. R. van der Westhuyzen, and F. C. de Beer. Remodeling of HDL remnants generated by scavenger receptor class B type I.

SR-BI-mediated selective lipid uptake segregates apoA-I and apoA-II catabolism

“…As reported previously (2,3), in this model system exogenously administered HDL 2 became progressively smaller, with the formation of HDL remnants occurring in incremental steps ( Fig. 2A ).…”

“…The production of SR-BI-generated HDL remnants in apoA-I Ϫ / Ϫ mice was described previously (2,3). ApoA-I Ϫ / Ϫ mice weighing at least 25 g were injected in the tail vein with 1.5 ϫ 10 11 particles of AdSR-BI, a replication-defective adenoviral vector expressing mouse SR-BI.…”

“…SR-BI-mediated selective lipid uptake generates incrementally smaller and denser HDL particles (HDL remnants) depleted in CE (2). These HDL remnants generated by SR-BI are mostly converted to larger particles by rapidly reassociating with existing HDL particles in the plasma in an enzyme-independent manner (2,3). A portion of the HDL remnant apolipoprotein, however, is directed toward catabolism (2).…”

“…It has further been shown that apoA-II inhibits HDL remodeling mediated by CETP (18). To study the fate of apoA-II during HDL remnant metabolism, we used an established model that involves injecting a bolus (750 g) of radiolabeled human HDL 2 into apolipoprotein A-I-deficient (apoA-I Ϫ / Ϫ ) mice with adenovirally mediated overexpression of SR-BI and then analyzing the remnant HDL particles that accumulate in the plasma of these mice (2,3). The apolipoprotein composition of HDL remnants processed to different extents by SR-BI was determined.…”

Scavenger Receptor BI-mediated Selective Uptake Is Required for the Remodeling of High Density Lipoprotein by Endothelial Lipase

“…Importantly, SR-BI mediates selective uptake of cholesteryl ester out of HDL particles into the liver and the adrenals in vivo (15,18,19). Although the selective uptake by SR-BI might play a central role in the remodeling of HDL (20), the dependence of EL-mediated remodeling and catabolism of HDL on functional SR-BI expression has not been experimentally addressed thus far.…”