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Expression of chemokine (C-C motif) ligand 18 in human macrophages and atherosclerotic plaques

Artikel i vetenskaplig tidskrift
Författare Daniel Hägg
Fredrik J. Olson
Josefin Kjelldahl
Margareta Jernås
Dag Thelle
Lena M S Carlsson
Björn Fagerberg
Per-Arne Svensson
Publicerad i Atherosclerosis
Volym 204
Nummer/häfte 2
Sidor e15-20
ISSN 1879-1484
Publiceringsår 2009
Publicerad vid Institutionen för medicin, avdelningen för molekylär och klinisk medicin
Sidor e15-20
Språk en
Länkar dx.doi.org/10.1016/j.atherosclerosi...
Ämnesord Aged, Biological Markers/blood, Carotid Artery Diseases/*genetics/immunology/surgery, Case-Control Studies, Chemokines, CC/blood/*genetics, Coronary Disease/genetics/immunology, Endarterectomy, Carotid, Female, Gene Expression Profiling/methods, Gene Frequency, Humans, Immunohistochemistry, Macrophages/*immunology, Male, Middle Aged, Oligonucleotide Array Sequence Analysis, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Promoter Regions, Genetic
Ämneskategorier Molekylär medicin (genetik och patologi)

Sammanfattning

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. CONCLUSION: CCL18 is predominantly expressed in human atherosclerotic plaques and may participate in the atherosclerotic plaque formation.

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