Expression of chemokine (C-C motif) ligand 18 in human macrophages and atherosclerotic plaques.
OBJECTIVE
Using gene expression profiling, we aimed to identify genes that are predominantly expressed in human carotid atherosclerotic plaques. Such genes may be important in atherogenesis and pathophysiology of the plaque, and genes that encode for secreted proteins may be potential biomarkers for atherosclerosis and cardiovascular disease.


METHODS
DNA microarray generated expression profiles of human carotid atherosclerotic plaques were compared to expression profiles of 80 different human tissues and cell types, to identify plaque-specific genes.


RESULTS
We identified the chemokine (C-C motif) ligand 18 (CCL18) as predominantly expressed in human carotid plaque. Immunohistochemistry showed that CCL18 protein was localized to a subset of macrophages in carotid plaques. Monocyte-derived macrophages from subjects with atherosclerosis had threefold higher expression of CCL18 than macrophages from control subjects (p=0.012). Subjects with A/G genotype of the rs2015086 SNP in the promoter region of the CCL18 gene had threefold higher macrophage expression of CCL18 than subjects with A/A genotype (p=0.049), but we found no association of this SNP with an increased risk of coronary heart disease. We also compared serum levels of CCL18 from subjects with symptomatic carotid artery disease with control subjects. There were no differences in serum levels of CCL18 between the two groups, however CCL18 correlated with measurements of adiposity.


CONCLUSIONS
CCL18 is predominantly expressed in human atherosclerotic plaques and may participate in the atherosclerotic plaque formation.
Hägg
Daniel A
DA
Center of Metabolic and Cardiovascular Research, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Göteborg, Vita Stråket 15, 41345 Göteborg, Sweden. daniel.hagg@medic.gu.se
Olson
Fredrik J
FJ
Kjelldahl
Josefin
J
Jernås
Margareta
M
Thelle
Dag S
DS
Carlsson
Lena M S
LM
Fagerberg
Björn
B
Svensson
Per-Arne
PA
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002340:Carotid Artery Diseases / Q000235:genetics* / Q000276:immunology / Q000601:surgery; D016022:Case-Control Studies; D019742:Chemokines, CC / Q000097:blood / Q000235:genetics*; D003327:Coronary Disease / Q000235:genetics / Q000276:immunology; D016894:Endarterectomy, Carotid; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005787:Gene Frequency; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
D015415:Biomarkers; C111792:CCL18 protein, human; D019742:Chemokines, CC