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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:1599-1606.)
© 1995 American Heart Association, Inc.

Articles

Inhibition of Lecithin-Cholesterol Acyltransferase and Modification of HDL Apolipoproteins by Aldehydes

Mark R. McCall; Jean Y. Tang; John K. Bielicki; Trudy M. Forte

From the Department of Molecular and Nuclear Medicine, Life Sciences Division, Lawrence Berkeley Laboratory, University of California at Berkeley.

Correspondence to Mark R. McCall, PhD, Lawrence Berkeley Laboratory, Donner Laboratory, 1 Cyclotron Rd, Berkeley, CA 94720.

Abstract Experimental evidence suggests that aldehydes generated as a consequence of lipid peroxidation may be involved in the pathogenesis of atherosclerosis. It is well documented that aldehydes modify LDL; however, less is known concerning the effects of aldehydes on other plasma and interstitial fluid components. In the present study, we investigated the effects of five physiologically relevant aldehydes (acetaldehyde, acrolein, hexanal, 4-hydroxynonenal [HNE], and malondialdehyde [MDA]) on two key constituents of the antiatherogenic reverse cholesterol transport pathway, lecithin-cholesterol acyltransferase (LCAT) and HDL. Human plasma was incubated for 3 hours at 37°C with each one of the five aldehydes at concentrations ranging from 0.16 to 84 mmol/L. Dose-dependent decreases in LCAT activity were observed. The short-chain (acrolein) and long-chain (HNE) ,ß-unsaturated aldehydes were the most effective LCAT inhibitors. Micromolar concentrations of these unsaturated aldehydes resulted in significant reductions in plasma LCAT activity. The short- and longer-chain saturated aldehydes acetaldehyde and hexanal and the dialdehyde MDA were considerably less effective at inhibiting LCAT than were acrolein and HNE. In addition to inhibiting LCAT, aldehydes increased HDL electrophoretic mobility and cross-linked HDL apolipoproteins. Cross-linking of apolipoproteins A-I and A-II required higher aldehyde concentrations than inhibition of LCAT. The ,ß-unsaturated aldehydes acrolein and HNE were fourfold to eightfold more effective cross-linkers of apolipoproteins A-I and A-II than the other aldehydes studied. These data suggest that products of lipid peroxidation, especially unsaturated aldehydes, may interfere with normal HDL cholesterol transport by inhibiting LCAT and modifying HDL apolipoproteins.

Key Words: lecithin-cholesterol acyltransferase • reverse cholesterol transport • apolipoproteins A-I and A-II • ,ß-unsaturated aldehydes • HDL

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