Chemokines: key regulators of mononuclear cell recruitment in atherosclerotic vascular disease.
Understanding the increasingly complex role of chemokines in various manifestations of atherosclerotic vascular disease and the apparent redundancy in their expression requires improved concepts defining the specialization and cooperation of chemokines in regulating the recruitment of mononuclear cells to vascular lesions. In an attempt to elaborate such models, this review highlights recent insights into the functional role of chemokines in mediating distinct steps during the atherogenic recruitment of monocytes and T cells obtained in genetically deficient mice and in suitable models. A particular focus is placed on the contribution of platelet chemokines deposited on endothelium for monocyte arrest, on differences in the involvement of chemokines between recruitment to native lesions and to neointimal lesions after arterial injury, and on closely related functions of macrophage migration inhibitory factor, a cytokine with considerable structural homology to chemokines. As an evolving aspect of atherosclerotic vascular disease, a role of chemokines, foremost stromal cell-derived factor-1alpha, in the recruitment of mononuclear progenitors of vascular cells during neointimal hyperplasia, endothelial recovery, and angiogenesis is discussed. The functional diversity and pleiotropy of chemokines in and beyond mononuclear cell recruitment awaits further elucidation to enable therapeutic targeting of atherogenesis by context-specific blockade of nonoverlapping chemokine receptor pairs.
Weber
Christian
C
Kardiovaskuläre Molekularbiologie, Universitätsklinikum Aachen, Rheinisch-Westfälische Technische Hochschule Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany. cweber@ukaachen.de
Schober
Andreas
A
Zernecke
Alma
A
D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology*; D018925:Chemokines / Q000502:physiology*; D006801:Humans; D009000:Monocytes / Q000502:physiology*
D018925:Chemokines