on October 23, 2003
Published online before print October 23, 2003, doi: 10.1161/01.ATV.0000102551.91154.96
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Submitted on September 24, 2003
Accepted on October 6, 2003
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 ;
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.
* To whom correspondence should be addressed. 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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