Increased levels of the homeostatic chemokine CXCL13 in human atherosclerosis - Potential role in plaque stabilization

Linda M. Smedbakken, Bente Halvorsen*, Isabelle Daissormont, Trine Ranheim, Annika E. Michelsen, Mona Skjelland, Ellen Lund Sagen, Lasse Folkersen, Kirsten Krohg-Sorensen, David Russell, Sverre Holm, Thor Ueland, Borre Fevang, Ulf Hedin, Arne Yndestad, Lars Gullestad, Goran K. Hansson, Erik A. Biessen, Pal Aukrust

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

23 Citations (Web of Science)

Abstract

Objectives: 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-beta, and interleukin-10 expression in THP-1 cells and in samples from isolated carotid plaques. Conclusion: 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.
Original languageEnglish
Pages (from-to)266-273
JournalAtherosclerosis
Volume224
Issue number1
DOIs
Publication statusPublished - Sep 2012

Keywords

  • Atherosclerosis
  • Stroke
  • Inflammation
  • Chemokines
  • Apoptosis

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