Shear stress-induced changes in atherosclerotic plaque composition are modulated by chemokines

Caroline Cheng, Dennie Tempel, Rien van Haperen, Hetty C de Boer, Dolf Segers, Martin Huisman, Anton Jan van Zonneveld, Pieter J M Leenen, Anton van der Steen, Patrick W Serruys, Rini de Crom, Rob Krams

Research output: Contribution to journalArticleAcademicpeer-review


We previously found that low shear stress (LSS) induces atherosclerotic plaques in mice with increased lipid and matrix metalloproteinase content and decreased vascular smooth muscle and collagen content. Here, we evaluated the role of chemokines in this process, using an extravascular device inducing regions of LSS, high shear stress, and oscillatory shear stress (OSS) in the carotid artery. One week of shear stress alterations induced expression of IFN-gamma-inducible protein-10 (IP-10) exclusively in the LSS region, whereas monocyte chemoattractant protein-1 (MCP-1) and the mouse homolog of growth-regulated oncogene alpha (GRO-alpha) were equally upregulated in both LSS and OSS regions. After 3 weeks, GRO-alpha and IP-10 were specifically upregulated in LSS regions. After 9 weeks, lesions with thinner fibrous caps and larger necrotic cores were found in the LSS region compared with the OSS region. Equal levels of MCP-1 expression were observed in both regions, while expression of fractalkine was found in the LSS region only. Blockage of fractalkine inhibited plaque growth and resulted in striking differences in plaque composition in the LSS region. We conclude that LSS or OSS triggers expression of chemokines involved in atherogenesis. Fractalkine upregulation is critically important for the composition of LSS-induced atherosclerotic lesions.

Original languageEnglish
Pages (from-to)616-26
Number of pages11
JournalJournal of Clinical Investigation
Issue number3
Publication statusPublished - 2007


  • Animals
  • Apolipoproteins E
  • Atherosclerosis
  • Carotid Arteries
  • Carotid Artery Diseases
  • Chemokines
  • Gene Expression
  • Mice
  • Mice, Mutant Strains
  • Receptors, Cytokine
  • Receptors, HIV
  • Shear Strength
  • Stress, Mechanical


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