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Journal of Lipid Research, Vol. 48, 1792-1800, August 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Proteinuria increases oxylipid concentrations in VLDL and HDL but not LDL particles in the rat

John W. Newman^1,*,,, George A. Kaysen^**,, Bruce D. Hammock^, and Gregory C. Shearer^**,

^* Western Human Nutrition Research Center, United States Department of Agriculture
Department of Nutrition, University of California Davis, Davis, CA
Department of Entomology, University of California Davis, Davis, CA
^** Department of Internal Medicine, University of California Davis, Davis, CA
UC Davis Cancer Center, University of California Davis, Davis, CA
Department of Veterans Affairs, Northern California Health Care System, Mather, CA

Published, JLR Papers in Press, May 11, 2007.

¹ To whom correspondence should be addressed. e-mail: jnewman{at}whnrc.usda.gov

We previously established that proteinuria alters the apolipoprotein content of lipoproteins. This study was conducted to establish whether proteinuria also alters the concentrations of oxidized lipids within lipoprotein density fractions. To this end, we induced passive Heymann nephritis in Sprague Dawley rats and measured an array of alkaline-stable oxylipids in VLDL, LDL, and HDL particles. Proteinuria increased the total oxylipid amounts in the HDL and VLDL fractions. More importantly, these levels were increased when expressed per unit lipoprotein protein, indicating that the oxidized lipid load per particle was increased. Epoxides and diols increased 2-fold in HDL and 5-fold in VLDL, whereas LDL showed 2-fold decreases. The hydroxyeicosatetraenoic acids and hydroxyoctadecadienoic acids (HODEs) increased >4-fold in HDL and >20-fold in VLDL, whereas LDL showed 2-fold decreases in the HODEs. Therefore, nephrotic syndrome alters the lipoprotein oxylipid composition independently of an increase in total lipoprotein levels. These proteinuria-induced changes may be associated with the cardiovascular risk of lipoprotein oxidation.

Supplementary key words hyperlipidemia • metabolic profiling • eicosanoids • octadecanoids • nephrotic syndrome • oxylipin • lipoprotein

Abbreviations: apoA-I, apolipoprotein A-I; CUDA, 1-cyclohexylureido,3-dodecanoic acid; EET, epoxyeicosatrienoic acid; EpOME, epoxyoctadecamonoenoic acid; DHET, dihydroxyeicosatrieneoic acid; DHOME, dihydroxyoctadecamonoenoic acid; HETE, hydroxyeicosatetraenoic acid; HODE, hydroxyoctadecadienoic acid; HPLC/ESI-TOF, HPLC electrospray ionization time-of-flight; LpL, lipoprotein lipase; MS, mass spectroscopy; TGRL, triglyceride-rich lipoprotein; TG, triglyceride

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