title: Shear stress-induced changes in atherosclerotic plaque composition are modulated by chemokines.
abstract: 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.
authors.affiliation: Department of Cardiology, Thoraxcenter, Rotterdam, The Netherlands.
authors.forename: Caroline
authors.initials: C
authors.lastname: Cheng
authors.forename: Dennie
authors.initials: D
authors.lastname: Tempel
authors.forename: Rien
authors.initials: R
authors.lastname: van Haperen
authors.forename: Hetty C
authors.initials: HC
authors.lastname: de Boer
authors.forename: Dolf
authors.initials: D
authors.lastname: Segers
authors.forename: Martin
authors.initials: M
authors.lastname: Huisman
authors.forename: Anton Jan
authors.initials: AJ
authors.lastname: van Zonneveld
authors.forename: Pieter J M
authors.initials: PJ
authors.lastname: Leenen
authors.forename: Anton
authors.initials: A
authors.lastname: van der Steen
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Serruys
authors.forename: Rini
authors.initials: R
authors.lastname: de Crom
authors.forename: Rob
authors.initials: R
authors.lastname: Krams
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000209:etiology* / Q000473:pathology; D000073883:CX3C Chemokine Receptor 1; D002339:Carotid Arteries / Q000737:chemistry / Q000473:pathology*; D002340:Carotid Artery Diseases / Q000209:etiology* / Q000473:pathology; D018925:Chemokines / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D051379:Mice; D008817:Mice, Mutant Strains; D018121:Receptors, Cytokine / Q000032:analysis; D015728:Receptors, HIV / Q000032:analysis; D033081:Shear Strength; D013314:Stress, Mechanical
chemical_list: D001057:Apolipoproteins E; D000073883:CX3C Chemokine Receptor 1; D018925:Chemokines; D018121:Receptors, Cytokine; D015728:Receptors, HIV