Lipoprotein lipase facilitated uptake of LDL is mediated by the LDL receptor

Britta Loeffler, Joerg Heeren, Mareike Blaeser, Herbert Radner, Daniel Kayser, Birol Aydin, and Martin Merkel

III. Department of Internal Medicine, University Hospital Hamburg-Eppendorf, Hamburg 20251

Corresponding Author: merkel{at}uke.uni-hamburg.de

Lipoprotein lipase (LPL) mediates uptake of lipoproteins into different cell types independent of its catalytic activity. The mechanism of this process and its physiological relevance is not clear. Taking into account the importance of the endothelial barrier for lipoprotein uptake, in vitro studies with primary aortic endothelial cells from wild type and LDL receptor deficient (LDLR-/-) mice were performed. Addition of LPL almost doubled the uptake of LDL into wild type cells. However, there was virtually no LPL mediated change of LDL uptake into LDLR-/- cells. Upregulation of LDLR by LPDS/lovastatin in wild type cells resulted in a 7fold increase of LPL mediated LDL uptake. Uptake of chylomicron remnants was not affected by LDLR expression. In proteoglycan deficient cells, LPL did not increase uptake of lipoproteins. The physiological relevance of this pathway was studied in mice being both LDLR-/- and transgenic for catalytically inactive LPL in muscle. In the presence of LDLR, inactive LPL reduced LDL cholesterol significantly (13-24%). In the absence of LDLR, LDL cholesterol was not affected by transgenic LPL. Metabolic studies showed that in the presence of LDLR, LPL increased muscular uptake of LDL by 77%. In the absence of LDLR, transgenic LPL did not augment LDL uptake. Chylomicron uptake was not affected by the LDLR genotype. It is concluded, that LPL mediated cellular uptake of LDL, but not of chylomicrons, is dependent on the presence of both LDLR and proteoglycans.

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

M. Hisamatsu-Sakamoto, N. Sakamoto, and A. S. Rosenberg
Embryonic Stem Cells Cultured in Serum-Free Medium Acquire Bovine Apolipoprotein B-100 from Feeder Cell Layers and Serum Replacement Medium
Stem Cells, January 1, 2008; 26(1): 72 - 78.
[Abstract] [Full Text] [PDF]

G. Qiu and J. S. Hill
Endothelial lipase enhances low density lipoprotein binding and cell association in THP-1 macrophages
Cardiovasc Res, December 1, 2007; 76(3): 528 - 538.
[Abstract] [Full Text] [PDF]

All ASBMB Journals	Journal of Biological Chemistry
Molecular and Cellular Proteomics	ASBMB Today

				G. Qiu and J. S. Hill Endothelial lipase enhances low density lipoprotein binding and cell association in THP-1 macrophages Cardiovasc Res, December 1, 2007; 76(3): 528 - 538. [Abstract] [Full Text] [PDF]