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- Title
Acrolein Modifies Apolipoprotein A-I in the Human Artery Wall.
- Authors
SHAO, BAOHAI; O'BRIEN, KEVIN D.; MCDONALD, THOMAS O.; FU, XIAOYUN; ORAM, JOHN F.; UCHIDA, KOJI; HEINECKE, JAY W.
- Abstract
Carbonyl stress is implicated in accelerated vascular disease, but little is known about the factors that control the reactions of carbonyls with proteins. Acrolein is a reactive carbonyl generated by the oxidation of lipids and amino acids. It also forms during cigarette smoking. We therefore investigated the possibility that acrolein might react with apolipoprotein A-I (apoAI), the major protein of high-density lipoprotein (HDL), which plays a critical role in mobilizing cholesterol from artery wall macrophages. Tandem mass spectrometric analysis demonstrated that lysine residues were the only amino acids in apoA-I that were modified by acrolein. Immunohistochemical studies with a monoclonal antibody revealed that acrolein adducts colocalized with apoA-I in human atherosclerotic lesions. Moreover, the ability of apoA-I to remove cholesterol from cultured cells was impaired after exposure to acrolein, suggesting that the carbonyl might interfere with apoA-I's normal function of promoting cholesterol efflux from artery wall cells. Our observations suggest that acrolein may interfere with normal HDL cholesterol transport by modifying apoA-I. This structural damage might play a critical role in atherogenesis by impairing cholesterol removal from artery wall cells.
- Subjects
APOLIPOPROTEINS; BLOOD lipoproteins; AMINO acids; ALDEHYDES; ACROLEIN; ISOPENTENOIDS
- Publication
Annals of the New York Academy of Sciences, 2005, Vol 1043, Issue 1, p396
- ISSN
0077-8923
- Publication type
Article
- DOI
10.1196/annals.1333.046