Endotoxin-Lipoprotein Complex Formation as a Factor in Atherogenesis: Associations with Hyperlipidemia and with Lecithin:Cholesterol Acyltransferase Activity

Y. Sh. Schwartz^1,2* and M. I. Dushkin^1,2

¹Institute of Internal Medicine, Siberian Division of the Russian Academy of Medical Sciences, ul. Vladimirovskii Spusk 2a, Novosibirsk, 630003 Russia; fax: (3832) 29-3253

²Institute of Clinical Immunology, Siberian Division of the Russian Academy of Medical Sciences, ul. Yadrintsevskaya 14, Novosibirsk, 630090 Russia; fax: (3832) 22-7028; E-mail: YShSchwartz@mail.ru

^* To whom correspondence should be addressed.

Received December 10, 2001; Revision received March 27, 2002

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A potential role of endotoxin-lipoprotein (bacterial lipopolysaccharide-lipoprotein, LPS-LP) complex formation as a pathogenic factor for atherosclerosis has not been studied yet. The aim of this study was to test the hypothesis that in endotoxinemia in humans hyperlipidemia associated with atherosclerosis development can favor an excessive LPS-LP complex formation, and endotoxin presented in blood can inhibit lecithin:cholesterol acyltransferase (LCAT), one of the key enzymes of reverse cholesterol transport. Endotoxin-binding capacity of lipoproteins (LP) in patients with normolipidemia and hyperlipidemia types IIa and IV was estimated from label incorporation into different LP fractions isolated by means of sequential ultracentrifugation following serum preincubation with Salmonella minnesota R595 ¹²⁵I-labeled LPS. The effect of varied concentrations of S. minnesota R595 LPS on LCAT activity was evaluated from the overall esterifying activity of serum using [1,2-³H₂]cholesterol-labeled substrate. The elevation of low density LP (LDL) and very low density LP (VLDL) contents in blood serum in hyperlipidemia types IIa and IV, respectively, resulted in significant elevation of LPS binding to these fractions. LPS added to the blood serum leads to the dose-dependent decrease in LCAT activity. The revealed phenomena of elevated LPS binding to atherogenic LP fractions in hypercholesterolemia and endotoxin-induced LCAT inhibition suggest the pathogenic role of LPS-LP complexes in atherogenesis.

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KEY WORDS: atherosclerosis, endotoxin, lipoproteins, endotoxin-binding capacity, endotoxin-lipoprotein complex, lecithin:cholesterol acyltransferase

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