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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:2235.)
© 2003 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Gene Expression in Macrophage-Rich Inflammatory Cell Infiltrates in Human Atherosclerotic Lesions as Studied by Laser Microdissection and DNA Array

Overexpression of HMG-CoA Reductase, Colony Stimulating Factor Receptors, CD11A/CD18 Integrins, and Interleukin Receptors

Tiina T. Tuomisto; Anna Korkeela; Juha Rutanen; Helena Viita; Jan H. Bräsen; Mervi S. Riekkinen; Tuomas T. Rissanen; Kari Karkola; Zsolt Kiraly; Konrad Kölble; Seppo Ylä-Herttuala

From the A.I. Virtanen Institute (T.T.T., A.K., J.R., H.V., M.R., T.T.R., S.Y.-H.), Department of Medicine (S.Y.-H.), Gene Therapy Unit (S.Y.-H.), and Department of Pathology (K.K.), University of Kuopio, Kuopio, Finland; Franz Volhard Clinic, Charité, Humboldt University Hospital (J.H.B.), Berlin, Germany; Cardiovascular Surgery, University Hospital Eppendorf (Z.K.), Hamburg, Germany; Max-Delbrück-Centrum für Molekulare Medizin & Institut für Pathologie, Universitätsklinikum Charité (K.K.), Berlin, Germany.

Correspondence to Seppo Ylä-Herttuala, MD, PhD, FESC, Professor of Molecular Medicine, A.I. Virtanen Institute, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland. E-mail Seppo.Ylaherttuala{at}uku.fi

Objective— Inflammatory cells play an important role in atherogenesis. However, more information is needed about their gene expression profiles in human lesions.

Methods and Results— We used laser microdissection (LMD) to isolate macrophage-rich shoulder areas from human lesions. Gene expression profiles in isolated cells were analyzed by cDNA array and compared with expression patterns in normal intima and THP-1 macrophages. Upregulation of 72 genes was detected with LMD and included 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, interferon regulatory factor-5 (IRF-5), colony stimulating factor (CSF) receptors, CD11a/CD18 integrins, interleukin receptors, CD43, calmodulin, nitric oxide synthase (NOS), and extracellular superoxide dismutase (SOD). Several of these changes were also present in PMA-stimulated THP-1 macrophages in vitro. On the other hand, expression of several genes, such as VEGF, tissue factor pathway inhibitor 2, and apolipoproteins C-I and C-II, decreased.

Conclusions— Overexpression of HMG-CoA reductase in macrophage-rich lesion areas may explain some beneficial effects of statins, which can also modulate increased expression of CD11a/CD18 and CD43 found in microdissected cells. We also found increased expression of CSF receptors, IRF-5, and interleukin receptors, which could become useful therapeutic targets for the treatment of atherosclerotic diseases.

Key Words: atherosclerosis • genes • molecular biology • plaque • macrophages

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