Gadolinium Chloride-Induced Kupffer Cell Blockade Increases Uptake of Oxidized Low-Density Lipoproteins by Rat Heart and Aorta

I. F. Usynin^*, A. V. Khar'kovsky, N. I. Balitskaya, and L. E. Panin

Institute of Biochemistry, Siberian Branch of the Russian Academy of Medical Sciences, ul. Akademika Timakova 2, Novosibirsk, 630117 Russia; E-mail: ibhc@cyber.ma.nsc.ru

^* To whom correspondence should be addressed.

Received February 26, 1998; Revision received January 27, 1999

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Oxidized low-density lipoproteins (LDL) play a key role in the formation of atherosclerotic lesions of arteries. We analyzed the effect of hepatic resident macrophage (Kupffer cell) blockade on oxidized [¹²⁵I]LDL accumulation in different organs and tissues of the rat. Kupffer cell blockade was induced by gadolinium chloride (GdCl₃) which was injected intravenously 24 h prior to injection of oxidized [¹²⁵I]LDL into the rats. Ten minutes after administration to intact animals, oxidized [¹²⁵I]LDL was accumulated in the liver (86.8% of the dose administered), muscles (4.7%), spleen (2.1%), lungs (0.8%), kidney (0.6%), adrenal glands (0.2%), heart (0.15%), and thymus (0.04%). Kupffer cell blockade significantly decreased the clearance rate of oxidized [¹²⁵I]LDL from the blood. Specific radioactivity (per g tissue) decreased in the liver (1.3-fold compared to control), but increased in the aorta (2.5-fold), heart (2-fold), lungs (1.6-fold), and kidney (1.3-fold). The results indicate that the accumulation of oxidized LDL in heart and aorta significantly depends on the functional state of the mononuclear phagocyte system in the liver.

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KEY WORDS: oxidized low-density lipoproteins, Kupffer cells, macrophages, liver, gadolinium chloride, atherosclerosis

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