An Animal Model to Study Local Oxidation of LDL and Its Biological Effects in the Arterial Wall

From the King Gustaf V Research Institute, Karolinska Hospital (F.C., A.N., J.N., J.R.), and the Department of Cell and Molecular Biology, Karolinska Institute (J.T.), Stockholm, Sweden; the Department of Medical Laboratory Sciences and Technology, Division of Clinical Chemistry, Huddinge University Hospital, Huddinge, Sweden (U.D.); the Atherosclerosis Research Center, Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center and UCLA School of Medicine, Los Angeles (P.D., P.K.S., B.C.); and the Department of Medicine, University of California, San Diego (J.L.W., W.P.), Calif.

Correspondence to Federico Calara, King Gustaf V Research Institute, Karolinska Hospital, S-171 76 Stockholm, Sweden. E-mail rcalara{at}instmed.ks.se

Abstract—Oxidized LDL (oxLDL) is present in atherosclerotic lesions and is believed to play a key role in atherogenesis. Mainly on the basis of cell culture studies, oxLDL has been shown to produce many biological effects that influence the atherosclerotic process. To study LDL oxidation in vivo, we have established a model in which Sprague-Dawley rats are given a single injection of unmodified human LDL (4 mg/kg body weight ). Within 6 hours, an accumulation of apolipoprotein B and epitopes present on oxLDL are detected in the arterial endothelium and media. The presence of oxLDL is associated with activation of the transcription factor nuclear factor-B in the endothelium as well as endothelial expression of intercellular adhesion molecule-1. Injection of LDL enriched with the antioxidant probucol resulted in arterial accumulation of apolipoprotein B, but the expression of oxLDL-specific epitopes was reduced at 24 hours. Thus, this simple model has the potential to analyze the mechanisms behind and biological effects of LDL oxidation in vivo.

Key Words: atherosclerosis • oxLDL • nuclear factor-B • intercellular adhesion molecule-1

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