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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:1615.)
© 2003 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Temporal Relationships Between Circulating Levels of CC and CXC Chemokines and Developing Atherosclerosis in Apolipoprotein E*3 Leiden Mice

Nuala Murphy; K. Richard Bruckdorfer; David C. Grimsditch; Philip Overend; Martin Vidgeon-Hart; Pieter H.E. Groot; G. Martin Benson; Annette Graham

From the Department of Biochemistry and Molecular Biology (N.M., K.R.B., A.G.), Royal Free and University College Medical School of UCL, London; Atherosclerosis Department (D.C.G., P.H.E.G., G.M.B.), GlaxoSmithKline, Herts; and Statistical Sciences (P.O.) and Neurobiology (M.V.-H.) Departments, GlaxoSmithKline, Essex, UK.

Correspondence to Dr G. Martin Benson, Atherosclerosis Department, GlaxoSmithKline, Gunnels Wood Rd, Stevenage, Herts SG1 2NY, UK. E-mail g_martin_benson{at}gsk.com

Objectives— CC and CXC chemokines are implicated in leukocyte recruitment during development of atherosclerotic lesions, suggesting circulating levels of chemokines may be useful serum markers of atherogenesis. Serum chemokine concentrations were measured in apolipoprotein (apo) E*3 Leiden mice and their nontransgenic littermates and related to the differing rates of atherogenesis in these animals.

Methods and Results— Mice were fed a high-fat, high-cholesterol/cholate (HFC/C) diet for 18 weeks. Circulating levels of JE/monocyte chemotactic protein-1 increased (P<0.05) after 2 to 4 weeks, coincident with development of diet-induced hypercholesterolemia, and remained elevated throughout the study. Circulating KC concentrations increased (P<0.05) after consumption of HFC/C diet; however, unlike JE, serum KC concentrations increased more rapidly in apoE*3 Leiden mice than their nontransgenic littermates. Hepatic expression of JE and KC mRNA were detected by in situ hybridization in all mice fed HFC/C diet. Aortic expression of JE mRNA was seen only in apoE*3 Leiden mice within macrophage-rich atherosclerotic lesions. By contrast, no aortic expression of KC mRNA was detected by in situ hybridization.

Conclusions— Increases in serum chemokine concentrations did not reflect temporal aortic production of these molecules and proved less predictive than serum cholesterol of the markedly different extent of atheroma in apoE*3 Leiden and nontransgenic mice.

Key Words: chemokine • KC • JE • atherosclerosis • mice

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