Submitted on February 22, 2005
Revised on July 13, 2005
Accepted on July 21, 2005
SR-BI-mediated selective lipid uptake segregates apoA-1 and apoA-II catabolism
Maria C. de Beer, Deneys R. van der Westhuyzen, Nathan L. Whitaker, Nancy R. Webb, and Frederick C. de Beer
Internal Medicine, University of Kentucky, Kentucky Clinic, Lexington, KY 40536
Corresponding Author: fcdebe1{at}uky.edu
The HDL receptor SR-BI binds HDL and mediates selective uptake of cholesterol ester. We previously showed that remnants, produced when human HDL2 is catabolized in mice over expressing SR-BI, become incrementally smaller, ultimately consisting of small 
-migrating particles, distinct from pre-
HDL. When mixed with mouse plasma some remnant particles rapidly increase in size by associating with HDL without mediation of CETP, LCAT or PLTP. Here we show that processing of HDL2 by SR-BI over-expressing mice resulted in the preferential loss of apoA-II. Short term processing generated 2 distinct, small -migrating particles. One particle (8.0nm diameter) contained apoA-I and apoA-II; the other particle (7.7nm diameter) contained only apoA-I. With extensive SR-BI processing only the 7.7nm particle remained. Only the 8.0nm remnants were able to associate with HDL. Compared to HDL2 this remnant was more readily taken up by the liver than the kidney. We conclude that SR-BI-generated HDL remnants consist of particles with or without apoA-II and only those containing apoA-II associate with HDL in an enzyme independent manner. Extensive SR-BI processing generates small apoA-II-depleted particles unable to re-associate with HDL and readily taken up by the liver. This represents a pathway by which apoA-I and apoA-II catabolism are segregated.
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