Expression of chemokine (C-C motif) ligand 18 in human macrophages and atherosclerotic plaques
Journal article, 2009
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.
Polymorphism
Male
Carotid Artery Diseases/*genetics/immunology/surgery
Chemokines
Promoter Regions
Case-Control Studies
Carotid
Biological Markers/blood
Polymerase Chain Reaction
Aged
CC/blood/*genetics
Humans
Female
Macrophages/*immunology
Coronary Disease/genetics/immunology
Oligonucleotide Array Sequence Analysis
Gene Frequency
Immunohistochemistry
Endarterectomy
Middle Aged
Single Nucleotide
Gene Expression Profiling/methods
Genetic
Author
Daniel Hägg
University of Gothenburg
Fredrik J. Olson
University of Gothenburg
Josefin Kjelldahl
University of Gothenburg
Margareta Jernås
University of Gothenburg
D. S. Thelle
Lena M S Carlsson
University of Gothenburg
Björn Fagerberg
University of Gothenburg
Per-Arne Svensson
University of Gothenburg
Atherosclerosis
1879-1484 (ISSN)
Vol. 204 2 e15-20Subject Categories
Medical Genetics
DOI
10.1016/j.atherosclerosis.2008.10.010