TitleLdl modified by hypochlorous acid is a potent inhibitor of lecithin-cholesterol acyltransferase activity.
Publication TypeJournal Article
Year of Publication2001
AuthorsMcCall MR, Carr AC, Forte TM, Frei B
JournalArterioscler Thromb Vasc Biol
Date Published2001 Jun
KeywordsChloramines, Cysteine, Humans, Hypochlorous Acid, Lipid Peroxidation, Lipid Peroxides, Lipoproteins, LDL, Phosphatidylcholine-Sterol O-Acyltransferase

Modification of low density lipoprotein (LDL) by myeloperoxidase-generated HOCl has been implicated in human atherosclerosis. Incubation of LDL with HOCl generates several reactive intermediates, primarily N-chloramines, which may react with other biomolecules. In this study, we investigated the effects of HOCl-modified LDL on the activity of lecithin-cholesterol acyltransferase (LCAT), an enzyme essential for high density lipoprotein maturation and the antiatherogenic reverse cholesterol transport pathway. We exposed human LDL (0.5 mg protein/mL) to physiological concentrations of HOCl (25 to 200 micromol/L) and characterized the resulting LDL modifications to apolipoprotein B and lipids; the modified LDL was subsequently incubated with apolipoprotein B-depleted plasma (density >1.063 g/mL fraction), which contains functional LCAT. Increasing concentrations of HOCl caused various modifications to LDL, primarily, loss of lysine residues and increases in N-chloramines and electrophoretic mobility, whereas lipid hydroperoxides were only minor products. LCAT activity was extremely sensitive to HOCl-modified LDL and was reduced by 23% and 93% by LDL preincubated with 25 and 100 micromol/L HOCl, respectively. Addition of 200 micromol/L ascorbate or N-acetyl derivatives of cysteine or methionine completely prevented LCAT inactivation by LDL preincubated with

Alternate JournalArterioscler. Thromb. Vasc. Biol.
PubMed ID11397717
Grant ListHL-18574 / HL / NHLBI NIH HHS / United States
HL-49954 / HL / NHLBI NIH HHS / United States
HL-56170 / HL / NHLBI NIH HHS / United States
HL-60886 / HL / NHLBI NIH HHS / United States