title: Enhanced expression of the homeostatic chemokines CCL19 and CCL21 in clinical and experimental atherosclerosis: possible pathogenic role in plaque destabilization.
abstract: OBJECTIVE
  Based on their role in T-cell homing into nonlymphoid tissue, we examined the role of the homeostatic chemokines CCL19 and CCL21 and their common receptor CCR7 in coronary artery disease (CAD).
  
  
  RESULTS
  We performed studies in patients with stable (n=40) and unstable (n=40) angina and healthy controls (n=20), in vitro studies in T-cells and macrophages, and studies in apolipoprotein-E-deficient (ApoE-/-) mice and human atherosclerotic carotid plaques. We found increased levels of CCL19 and CCL21 within the atherosclerotic lesions of the ApoE-/- mice, in human atherosclerotic carotid plaques, and in plasma of CAD patients. Whereas strong CCR7 expression was seen in T-cells from murine and human atherosclerotic plaques, circulating T-cells from angina patients showed decreased CCR7 expression. CCL19 and CCL21 promoted an inflammatory phenotype in T-cells and macrophages and increased matrix metalloproteinase (MMP) and tissue factor levels in the latter cell type. Although aggressive statin therapy increased CCR7 and decreased CCL19/CCL21 levels in peripheral blood from CAD patients, conventional therapy did not.
  
  
  CONCLUSIONS
  The abnormal regulation of CCL19 and CCL21 and their common receptor in atherosclerosis could contribute to disease progression by recruiting T-cells and macrophages to the atherosclerotic lesions and by promoting inflammatory responses in these cells.
authors.affiliation: Research Institute for Internal Medicine, Rikshospitalet-Radiumhospitalet Medical Center, N-0027 Oslo, Norway. j.k.damas@medisin.uio.no
authors.forename: Jan K
authors.initials: JK
authors.lastname: Damås
authors.forename: Camilla
authors.initials: C
authors.lastname: Smith
authors.forename: Erik
authors.initials: E
authors.lastname: Øie
authors.forename: Børre
authors.initials: B
authors.lastname: Fevang
authors.forename: Bente
authors.initials: B
authors.lastname: Halvorsen
authors.forename: Torgun
authors.initials: T
authors.lastname: Waehre
authors.forename: Agnes
authors.initials: A
authors.lastname: Boullier
authors.forename: Unni
authors.initials: U
authors.lastname: Breland
authors.forename: Arne
authors.initials: A
authors.lastname: Yndestad
authors.forename: Olga
authors.initials: O
authors.lastname: Ovchinnikova
authors.forename: Anna-Karin L
authors.initials: AK
authors.lastname: Robertson
authors.forename: Wiggo J
authors.initials: WJ
authors.lastname: Sandberg
authors.forename: John
authors.initials: J
authors.lastname: Kjekshus
authors.forename: Kjetil
authors.initials: K
authors.lastname: Taskén
authors.forename: Stig S
authors.initials: SS
authors.lastname: Frøland
authors.forename: Lars
authors.initials: L
authors.lastname: Gullestad
authors.forename: Göran K
authors.initials: GK
authors.lastname: Hansson
authors.forename: Oswald
authors.initials: O
authors.lastname: Quehenberger
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
mesh_terms: D015906:Angioplasty, Balloon, Coronary / Q000379:methods; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D000069059:Atorvastatin; D001707:Biopsy, Needle; D002478:Cells, Cultured; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism*; D003327:Coronary Disease / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005786:Gene Expression Regulation; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear; D051379:Mice; D008822:Mice, Transgenic; D011379:Prognosis; D011758:Pyrroles / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000032:analysis; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism; D012016:Reference Values; D012307:Risk Factors; D012680:Sensitivity and Specificity; D019821:Simvastatin / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D001057:Apolipoproteins E; C515460:CCL19 protein, human; C515478:CCL21 protein, human; C515370:CCR7 protein, human; C515461:Ccl19 protein, mouse; C515479:Ccl21c protein, mouse; C515371:Ccr7 protein, mouse; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC; D006538:Heptanoic Acids; D011758:Pyrroles; D012333:RNA, Messenger; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D000069059:Atorvastatin; D019821:Simvastatin