Gene expression in macrophage-rich inflammatory cell infiltrates in human atherosclerotic lesions as studied by laser microdissection and DNA array

Item Type:	Article
Title:	Gene expression in macrophage-rich inflammatory cell infiltrates in human atherosclerotic lesions as studied by laser microdissection and DNA array
Creators Name:	Tuomisto, T.T. and Korkeela, A. and Rutanen, J. and Viita, H. and Braesen, J.H. and Riekkinen, M.S. and Rissanen, T.T. and Karkola, K. and Kiraly, Z. and Koelble, K. and Yla-Herttuala, S.
Abstract:	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.
Keywords:	Atherosclerosis, Genes, Molecular Biology, Plaque, Macrophages
Source:	Arteriosclerosis Thrombosis and Vascular Biology
ISSN:	1079-5642
Publisher:	American Heart Association
Volume:	23
Number:	12
Page Range:	2235-2240
Date:	December 2003
Official Publication:	https://doi.org/10.1161/01.ATV.0000102551.91154.96
PubMed:	View item in PubMed

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