Chemokines in Atherosclerosis

Abstract

Abstract-The fundamental importance of chemokines for atherogenesis, progression, and destabilization of atherosclerotic plaques is now widely appreciated, but the degree of complexity, specificity, and cooperativity harnessed by these signal molecules to govern atherogenic cell recruitment and homeostasis is still being refined. Since the role of chemokines in atherosclerotic vascular disease has been reviewed in this journal, significant progress has been accomplished in defining the regulation of chemokine expression and function in atherosclerosis. In this update, we will highlight these recent developments, in particular the identification of components regulating the transcriptional machinery of the proatherogenic chemokine CCL5, distinct roles of its receptors CCR1 and CCR5 in plaque formation and immunobalance, and differential site-and stage-specific effects of T cell-activating chemokines and their receptors, eg, CXCL10 and CXCR3. The contribution of the transmembrane chemokines CX 3 CL1 and CXCL16 with their respective receptors CX 3 CR1 and CXCR6 in the recruitment of T cell and monocyte subsets and shear-mediated plaque modulation will be discussed. Finally, the role of CXCR2 and CXCR4, their respective ligands CXCL1 and CXCL12, and the noncanonical dual agonist MIF in atheroprogression will be dissected.

Macrophage Migration Inhibitory Factor–CXCR4 Is the Dominant Chemotactic Axis in Human Mesenchymal Stem Cell Recruitment to Tumors

“…By activating CXCR4, MIF promotes T cell chemotaxis. Accordingly, numerous in vivo studies in proatherogenic mouse models have demonstrated that the MIF-CXCR4 axis critically contributes to atherogenic leukocyte recruitment and atheroprogression (26,(33)(34)(35). The MIF-CXCR4 axis also regulates endothelial progenitor cell migration and cancer cell metastasis (36)(37)(38).…”

CXCL4-Induced Macrophages: A Novel Therapeutic Target in Human Atherosclerosis?

“…Platelets and platelet-derived chemokines are important factors during atherogenesis (Gleissner et al 2008, von Hundelshausen et al 2007, Weber 2005, Weber 2008, Zernecke et al 2008). In 2003, Ley et al were able to demonstrate that activated platelets are able to promote atherogenesis (Huo et al 2003).…”

Erythrocyte Duffy antigen receptor for chemokines (DARC): diagnostic and therapeutic implications in atherosclerotic cardiovascular disease

“…In fact it seems that each stage of atherosclerosis is characterized by different chemokine-signalling [32] . In the early stages of atherosclerosis, oxLDL induces the expression of CCL2 (or monocyte chemoattractant protein 1) and CX3CL1, by vascular smooth muscle cells (SMCs) and endothelial cells (ECs) [32,33] .…”

“…In fact it seems that each stage of atherosclerosis is characterized by different chemokine-signalling [32] . In the early stages of atherosclerosis, oxLDL induces the expression of CCL2 (or monocyte chemoattractant protein 1) and CX3CL1, by vascular smooth muscle cells (SMCs) and endothelial cells (ECs) [32,33] . CX3CL1 is a structurally unique chemokine that acts both as a chemoattractant and as a potent adhesion molecule through a non-integrin-dependent mechanism [34][35][36] .…”