title: Increased levels of the homeostatic chemokine CXCL13 in human atherosclerosis - Potential role in plaque stabilization.
abstract: OBJECTIVE
  Based on the newly recognized role of the homeostatic chemokines in inflammation, we hypothesized that CXCL13 could modulate atherogenesis and plaque destabilization.
  
  
  METHODS
  The study included in vivo analyses in patients with carotid atherosclerosis and in vitro experiments in cells involved in atherogenesis (ie, monocytes/macrophages, vascular smooth muscle cells [SMC], and platelets).
  
  
  RESULTS
  Our main findings were: (i) Patients with carotid atherosclerosis (n = 130) had increased plasma levels of CXCL13 with particularly high levels in symptomatic disease. (ii) CXCL13 showed increased expression within atherosclerotic carotid plaques as compared with non-atherosclerotic vessels. (iii) Within the atherosclerotic lesions, CXCR5 and CXCL13 were expressed by macrophages and SMC in all stages of plaque progression. (iv) Releasate from activated platelets and toll-like receptor activation enhanced the expression of CXCL13 in THP-1 monocytes and primary monocytes. (v) In vitro, CXCL13 exerted anti-apoptotic effects in primary monocytes, THP-1 macrophages, and vascular SMC. (vi) CXCL13 increased arginase-1, transforming growth factor-β, and interleukin-10 expression in THP-1 cells and in samples from isolated carotid plaques.
  
  
  CONCLUSIONS
  Levels of CXCL13 are increased in carotid atherosclerosis both systemically and within the atherosclerotic lesion. Based on our in vitro findings, we hypothesize a potential plaque stabilizing effects of CXCL13-CXCR5 interaction.
authors: Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors: Linda M
authors: LM
authors: Smedbakken
authors: Bente
authors: B
authors: Halvorsen
authors: Isabelle
authors: I
authors: Daissormont
authors: Trine
authors: T
authors: Ranheim
authors: Annika E
authors: AE
authors: Michelsen
authors: Mona
authors: M
authors: Skjelland
authors: Ellen Lund
authors: EL
authors: Sagen
authors: Lasse
authors: L
authors: Folkersen
authors: Kirsten
authors: K
authors: Krohg-Sørensen
authors: David
authors: D
authors: Russell
authors: Sverre
authors: S
authors: Holm
authors: Thor
authors: T
authors: Ueland
authors: Børre
authors: B
authors: Fevang
authors: Ulf
authors: U
authors: Hedin
authors: Arne
authors: A
authors: Yndestad
authors: Lars
authors: L
authors: Gullestad
authors: Göran K
authors: GK
authors: Hansson
authors: Erik A
authors: EA
authors: Biessen
authors: Pål
authors: P
authors: Aukrust
mesh_terms: D002340:Carotid Artery Diseases / Q000378:metabolism* / Q000473:pathology; D054382:Chemokine CXCL13 / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000378:metabolism / Q000473:pathology*; D054380:Receptors, CXCR5 / Q000378:metabolism*
chemical_list: C110663:CXCL13 protein, human; C095085:CXCR5 protein, human; D054382:Chemokine CXCL13; D054380:Receptors, CXCR5