title: Atherosclerotic Plaque Stability Is Affected by the Chemokine CXCL10 in Both Mice and Humans.
abstract: Background. The chemokine CXCL10 is specifically upregulated during experimental development of plaque with an unstable phenotype. In this study we evaluated the functional consequences of these findings in mice and humans. Methods and Results. In ApoE(-/-) mice, we induced unstable plaque with using a flow-altering device around the carotid artery. From week 1 to 4, mice were injected with a neutralizing CXCL10 antibody. After 9 weeks, CXCL10 inhibition resulted in a more stable plaque phenotype: collagen increased by 58% (P = 0.002), smooth muscle cell content increased 2-fold (P = 0.03), while macrophage MHC class II expression decreased by 50% (P = 0.005). Also, the size of necrotic cores decreased by 41% (P = 0.01). In 106 human carotid endarterectomy specimens we found that increasing concentrations of CXCL10 strongly associate with an increase in atheromatous plaque phenotype (ANOVA, P = 0.003), with high macrophage, low smooth muscle cell, and low collagen content. Conclusions. In the present study we showed that CXCL10 is associated with the development of vulnerable plaque in human and mice. We conclude that CXCL10 might provide a new lead towards plaque-stabilizing therapy.
authors.affiliation: Department of Cardiology, Erasmus University Medical Center, 3522ZZ Rotterdam, The Netherlands.
authors.forename: Dolf
authors.initials: D
authors.lastname: Segers
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Lipton
authors.forename: Pieter J M
authors.initials: PJ
authors.lastname: Leenen
authors.forename: Caroline
authors.initials: C
authors.lastname: Cheng
authors.forename: Dennie
authors.initials: D
authors.lastname: Tempel
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
authors.forename: Frans L
authors.initials: FL
authors.lastname: Moll
authors.forename: Rini
authors.initials: R
authors.lastname: de Crom
authors.forename: Rob
authors.initials: R
authors.lastname: Krams