Circulating transcriptome reveals markers of atherosclerosis.
Circulating monocytes mediate inflammation in atherosclerosis and may serve as easily accessible reporters of disease. To search for markers of atherosclerosis, we compared the in vivo transcriptomes of monocytes purified from patients undergoing carotid endarterectomy and normal subjects by using the serial analysis of gene expression technique. We selected a subset of differentially expressed monocyte-specific genes and confirmed their expression levels. The Finkel-Biskis-Jinkins osteosarcoma (FOS) gene was significantly increased in patients, and the highest levels of FOS associated with patients who had previously undergone coronary revascularization. The correlation between coronary revascularization and FOS was higher than that compared with the cardiac risk marker high sensitivity C-reactive protein. In vitro inhibition of FOS using small interfering RNA and 3-hydroxy-3-methyl-glutaryl CoA reductase inhibitor simvastatin (statin) affected monocyte activation and suggested an important role in pathogenesis. Given the prominent role of FOS in inflammation and calcification, its association with atherosclerosis severity has clear pathophysiologic bases as well as clinical implications as a marker. Our results suggest that analysis of gene expression in circulating cells may provide biological and clinical insights into human atherosclerosis, and that this type of approach may be applicable for studying other types of diseases.
Patino
Willmar D
WD
Cardiovascular Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10-CRC, 5 East, Room 5-5330, 10 Center Drive, Bethesda, MD 20892, USA.
Mian
Omar Y
OY
Kang
Ju-Gyeong
JG
Matoba
Satoaki
S
Bartlett
Linda D
LD
Holbrook
Brenda
B
Trout
Hugh H
HH
Kozloff
Louis
L
Hwang
Paul M
PM
D001161:Arteriosclerosis / Q000097:blood / Q000235:genetics*; D015153:Blotting, Western; D016022:Case-Control Studies; D006801:Humans; D007150:Immunohistochemistry; D012333:RNA, Messenger / Q000097:blood*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012269:Ribosomal Proteins / Q000235:genetics*
D012333:RNA, Messenger; D012269:Ribosomal Proteins; C076845:FAU protein, human
Blood. 1999 Aug 1;94(3):837-44
10419873
Nature. 1992 Dec 24-31;360(6406):741-5
1465144
Genome Res. 2000 Jul;10(7):1051-60
10899154
Science. 2000 Aug 18;289(5482):1197-202
10947988
J Clin Oncol. 2001 Jun 1;19(11):2948-58
11387368
Mol Cell. 2001 Mar;7(3):673-82
11463391
Circulation. 2002 Mar 5;105(9):1135-43
11877368
Nat Biotechnol. 2002 May;20(5):508-12
11981567
Nat Cell Biol. 2002 May;4(5):E131-6
11988758
JAMA. 2002 May 15;287(19):2570-81
12020339
Circ Res. 2002 Oct 4;91(7):565-9
12364383
Circulation. 2003 Jan 28;107(3):363-9
12551853
Am J Cardiol. 2003 May 1;91(9):1107-9
12714156
Int J Cardiol. 2003 Nov;92(1):59-63
14602218
JAMA. 2004 Jan 14;291(2):210-5
14722147
Mayo Clin Proc. 2004 Feb;79(2):197-210
14959915
J Rheumatol. 2004 Mar;31(3):464-9
14994389
N Engl J Med. 2004 Apr 8;350(15):1495-504
15007110
J Clin Invest. 2004 Apr;113(8):1234-42
15085203
Cell Signal. 2004 Jul;16(7):769-79
15115656
Am J Geriatr Cardiol. 2004 May-Jun;13(3):137-51
15133417
Circulation. 2004 Jun 1;109(21 Suppl 1):II2-10
15173056
J Immunol Methods. 2004 May;288(1-2):123-34
15183091
Arterioscler Thromb Vasc Biol. 2004 Sep;24(9):1676-81
15242861
J Clin Microbiol. 1995 Jun;33(6):1562-6
7650187
Cytometry. 1997 Oct 1;29(2):155-64
9332822
Genome Res. 1997 Oct;7(10):986-95
9331369
Int J Oncol. 1998 Mar;12(3):685-700
9472112
Mol Cell. 1998 Aug;2(2):275-81
9734366
N Engl J Med. 1999 Jan 14;340(2):115-26
9887164
Nat Med. 2004 Oct;10(10):1128-32
15448687
Science. 1966 Feb 11;151(3711):698-701
5218049
Int J Cancer. 1988 Mar 15;41(3):456-61
3162233
Annu Rev Cell Biol. 1990;6:539-57
2125830
Experientia. 1991 Jan 15;47(1):22-31
1999239
Cell. 1992 Nov 13;71(4):577-86
1423615
Nature. 1999 Oct 7;401(6753):616-20
10524633