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Biology 2015, 4(1), 17-38; doi:10.3390/biology4010017

Will Lipidation of ApoA1 through Interaction with ABCA1 at the Intestinal Level Affect the Protective Functions of HDL?

F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, CH-4070 Basel, Switzerland
Academic Editor: Annette Graham
Received: 9 October 2014 / Accepted: 18 December 2014 / Published: 6 January 2015
(This article belongs to the Special Issue Lipid Metabolism)
View Full-Text   |   Download PDF [850 KB, uploaded 6 January 2015]   |  

Abstract

The relationship between levels of high-density lipoprotein cholesterol (HDL-C) and cardiovascular (CV) risk is well recognized; however, in recent years, large-scale phase III studies with HDL-C-raising or -mimicking agents have failed to demonstrate a clinical benefit on CV outcomes associated with raising HDL-C, casting doubt on the “HDL hypothesis.” This article reviews potential reasons for the observed negative findings with these pharmaceutical compounds, focusing on the paucity of translational models and relevant biomarkers related to HDL metabolism that may have confounded understanding of in vivo mechanisms. A unique function of HDL is its ability to interact with the ATP-binding cassette transporter (ABC) A1 via apolipoprotein (Apo) A1. Only recently, studies have shown that this process may be involved in the intestinal uptake of dietary sterols and antioxidants (vitamin E, lutein and zeaxanthin) at the basolateral surface of enterocytes. This parameter should be assessed for HDL-raising drugs in addition to the more documented reverse cholesterol transport (RCT) from peripheral tissues to the liver. Indeed, a single mechanism involving the same interaction between ApoA1 and ABCA1 may encompass two HDL functions previously considered as separate: antioxidant through the intestinal uptake of antioxidants and RCT through cholesterol efflux from loaded cells such as macrophages. View Full-Text
Keywords: HDL; cholesterol; lutein; ABCA1; antioxidants; apolipoprotein; HDL metabolism HDL; cholesterol; lutein; ABCA1; antioxidants; apolipoprotein; HDL metabolism
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Niesor, E.J. Will Lipidation of ApoA1 through Interaction with ABCA1 at the Intestinal Level Affect the Protective Functions of HDL? Biology 2015, 4, 17-38.

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