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


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.
A.I. Virtanen Institute, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland.
Tiina T
TT
Tuomisto
Anna
A
Korkeela
Juha
J
Rutanen
Helena
H
Viita
Jan H
JH
Bräsen
Mervi S
MS
Riekkinen
Tuomas T
TT
Rissanen
Kari
K
Karkola
Zsolt
Z
Kiraly
Konrad
K
Kölble
Seppo
S
Ylä-Herttuala
D001161:Arteriosclerosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D040881:CD11a Antigen / Q000096:biosynthesis; D018821:CD18 Antigens / Q000096:biosynthesis; D002465:Cell Movement; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000096:biosynthesis*; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D016023:Integrins / Q000096:biosynthesis*; D007834:Lasers; D008264:Macrophages / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology*; D009000:Monocytes / Q000737:chemistry / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D016184:Receptors, Colony-Stimulating Factor / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000096:biosynthesis
D040881:CD11a Antigen; D018821:CD18 Antigens; D016023:Integrins; D011956:Receptors, Cell Surface; D016184:Receptors, Colony-Stimulating Factor; D018123:Receptors, Interleukin; D006903:Hydroxymethylglutaryl CoA Reductases