Novel candidate genes in unstable areas of human atherosclerotic plaques.
OBJECTIVE
Comparison of gene expression in stable versus unstable atherosclerotic plaque may be confounded by interpatient variability. The aim of this study was to identify differences in gene expression between stable and unstable segments of plaque obtained from the same patient.


RESULTS
Human carotid endarterectomy specimens were segmented and macroscopically classified using a morphological classification system. Two analytical methods, an intraplaque and an interplaque analysis, revealed 170 and 1916 differentially expressed genes, respectively using Affymetrix gene chip analysis. A total of 115 genes were identified from both analyses. The differential expression of 27 genes was also confirmed using quantitative-polymerase chain reaction on a larger panel of samples. Eighteen of these genes have not been associated previously with plaque instability, including the metalloproteinase, ADAMDEC1 (approximately 37-fold), retinoic acid receptor responder-1 (approximately 5-fold), and cysteine protease legumain (approximately 3-fold). Matrix metalloproteinase-9 (MMP-9), cathepsin B, and a novel gene, legumain, a potential activator of MMPs and cathepsins, were also confirmed at the protein level.


CONCLUSIONS
The differential expression of 18 genes not previously associated with plaque rupture has been confirmed in stable and unstable regions of the same atherosclerotic plaque. These genes may represent novel targets for the treatment of unstable plaque or useful diagnostic markers of plaque instability.
Papaspyridonos
Marianna
M
Academic Department of Surgery, Cardiovascular Division, King's College, First Floor North Wing, London SE1 7EH UK.
Smith
Alberto
A
Burnand
Kevin G
KG
Taylor
Peter
P
Padayachee
Soundrie
S
Suckling
Keith E
KE
James
Christian H
CH
Greaves
David R
DR
Patel
Lisa
L
D050197:Atherosclerosis / Q000235:genetics* / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D002401:Cathepsin B / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000235:genetics; D004730:Endothelium, Vascular / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D000099240:Asparaginyl Endopeptidase
D015415:Biomarkers; D002401:Cathepsin B; D003546:Cysteine Endopeptidases; D020780:Matrix Metalloproteinase 9; D012333:RNA, Messenger; D000099240:Asparaginyl Endopeptidase