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Acrolein impairs the cholesterol transport functions of high density lipoproteins. PLoS One 2015;10(4):e0123138

Date

04/08/2015

Pubmed ID

25849485

Pubmed Central ID

PMC4388475

DOI

10.1371/journal.pone.0123138

Scopus ID

2-s2.0-84927672521   19 Citations

Abstract

High density lipoproteins (HDL) are considered athero-protective, primarily due to their role in reverse cholesterol transport, where they transport cholesterol from peripheral tissues to the liver for excretion. The current study was designed to determine the impact of HDL modification by acrolein, a highly reactive aldehyde found in high abundance in cigarette smoke, on the cholesterol transport functions of HDL. HDL was chemically-modified with acrolein and immunoblot and mass spectrometry analyses confirmed apolipoprotein crosslinking, as well as acrolein adducts on apolipoproteins A-I and A-II. The ability of acrolein-modified HDL (acro-HDL) to serve as an acceptor of free cholesterol (FC) from COS-7 cells transiently expressing SR-BI was significantly decreased. Further, in contrast to native HDL, acro-HDL promotes higher neutral lipid accumulation in murine macrophages as judged by Oil Red O staining. The ability of acro-HDL to mediate efficient selective uptake of HDL-cholesteryl esters (CE) into SR-BI-expressing cells was reduced compared to native HDL. Together, the findings from our studies suggest that acrolein modification of HDL produces a dysfunctional particle that may ultimately promote atherogenesis by impairing functions that are critical in the reverse cholesterol transport pathway.

Author List

Chadwick AC, Holme RL, Chen Y, Thomas MJ, Sorci-Thomas MG, Silverstein RL, Pritchard KA Jr, Sahoo D

Authors

Yiliang Chen Assistant Professor in the Medicine department at Medical College of Wisconsin
Kirkwood A. Pritchard PhD Professor in the Surgery department at Medical College of Wisconsin
Daisy Sahoo PhD Vice Chair, Professor in the Medicine department at Medical College of Wisconsin
Roy L. Silverstein MD Chair, Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin
Mary Sorci Thomas PhD Professor in the Medicine department at Medical College of Wisconsin
Michael J. Thomas PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Acrolein
Animals
Biological Transport
COS Cells
Cholesterol
Chromatography, Thin Layer
Lipoproteins, HDL
Macrophages
Mice
Mice, Inbred C57BL
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a