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

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

Nyckelord

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

Polymorphism

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)