title: Contribution of homeostatic chemokines CCL19 and CCL21 and their receptor CCR7 to coronary artery disease.
abstract: OBJECTIVE
  Our aim was to identify the role of the homeostatic chemokines CCL19 and CCL21 and their common receptor CCR7 in atherogenesis and to study the relationships between CCL19, CCL21, and CCR7 gene variants and coronary artery disease in a Chinese Han population.
  
  
  RESULTS
  Immunohistochemical analysis of samples with atherosclerosis of various stages showed increased CCL19, CCL21, and CCR7 expression in atherosclerotic coronary plaques compared with nonatherosclerotic controls. Expression levels increased in positive correlation with coronary lesion stage. Cell adhesion assays confirmed that CCL19 promoted monocyte adhesion, which was induced by CCR7, to human umbilical vein endothelial cells, an effect partially antagonized by atorvastatin. After the human umbilical vein endothelial cells were treated with CCR7-neutralizing antibody, both CCL19- and CCL21-induced monocyte to human umbilical vein endothelial cell migration and CCL19-induced monocyte to human umbilical vein endothelial cell adhesion were abolished. The associations between genetic variants of CCL19, CCL21, CCR7, and coronary artery disease in a Chinese Han population were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The following single nucleotide polymorphisms were associated with coronary artery disease: CCL19 rs2227302, CCL21 rs2812377, and CCR7 rs588019. Individuals with the CCL19 rs2227302 T allele or CCL21 rs2812377 G allele had higher plasma CCL19 levels than those with C/C genotype and higher CCL21 levels than those with T/T genotype in both case and control subjects.
  
  
  CONCLUSIONS
  CCL19/CCL21-CCR7 is a novel homeostatic chemokine system that modulates human monocyte adhesion and migration, promoting atherogenesis. It is associated with coronary artery disease risk in Chinese Han individuals. These data suggest that the CCL19/CCL21-CCR7 axis plays an important role in atherosclerosis progression.
authors.affiliation: From the Cardiovascular Research Institute and Department of Cardiology, Shenyang Northern Hospital, Shenyang, China.
authors.forename: Wenzhi
authors.initials: W
authors.lastname: Cai
authors.affiliation: From the Cardiovascular Research Institute and Department of Cardiology, Shenyang Northern Hospital, Shenyang, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Tao
authors.affiliation: From the Cardiovascular Research Institute and Department of Cardiology, Shenyang Northern Hospital, Shenyang, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: From the Cardiovascular Research Institute and Department of Cardiology, Shenyang Northern Hospital, Shenyang, China.
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Tian
authors.affiliation: From the Cardiovascular Research Institute and Department of Cardiology, Shenyang Northern Hospital, Shenyang, China.
authors.forename: Tengfei
authors.initials: T
authors.lastname: Liu
authors.affiliation: From the Cardiovascular Research Institute and Department of Cardiology, Shenyang Northern Hospital, Shenyang, China.
authors.forename: Xueyao
authors.initials: X
authors.lastname: Feng
authors.affiliation: From the Cardiovascular Research Institute and Department of Cardiology, Shenyang Northern Hospital, Shenyang, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Bai
authors.affiliation: From the Cardiovascular Research Institute and Department of Cardiology, Shenyang Northern Hospital, Shenyang, China.
authors.forename: Chenghui
authors.initials: C
authors.lastname: Yan
authors.affiliation: From the Cardiovascular Research Institute and Department of Cardiology, Shenyang Northern Hospital, Shenyang, China. yalinghan@gmail.com.
authors.forename: Yaling
authors.initials: Y
authors.lastname: Han
mesh_terms: D000368:Aged; D000483:Alleles; D000069059:Atorvastatin; D002448:Cell Adhesion; D054415:Chemokine CCL19 / Q000235:genetics / Q000502:physiology*; D054421:Chemokine CCL21 / Q000235:genetics / Q000502:physiology*; D002634:Chemotaxis, Leukocyte; D002681:China / Q000453:epidemiology; D003324:Coronary Artery Disease / Q000208:ethnology / Q000235:genetics / Q000503:physiopathology*; D018450:Disease Progression; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005838:Genotype; D006538:Heptanoic Acids / Q000494:pharmacology; D006706:Homeostasis; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011758:Pyrroles / Q000494:pharmacology; D054400:Receptors, CCR7 / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
chemical_list: C515460:CCL19 protein, human; C515478:CCL21 protein, human; C515370:CCR7 protein, human; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008070:Lipopolysaccharides; D011758:Pyrroles; D054400:Receptors, CCR7; D000069059:Atorvastatin
keywords: atherosclerosis; coronary artery disease; monocytes; polymorphism; single nucleotide