Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:1997-2008
Published online before print August 19, 2004, doi: 10.1161/01.ATV.0000142812.03840.6f
Published online before print August 19, 2004, doi: 10.1161/01.ATV.0000142812.03840.6f
© 2004 American Heart Association, Inc.
Brief Reviews |
Chemokines
Key Regulators of Mononuclear Cell Recruitment in Atherosclerotic Vascular Disease
From Kardiovaskuläre Molekularbiologie, Universitätsklinikum Aachen, Rheinisch-Westfälische Technische Hochschule Aachen, Aachen, Germany.
Correspondence to Christian Weber Kardiovaskuläre Molekularbiologie, Universitätsklinikum Aachen, Rheinisch-Westfälische Technische Hochschule Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany. E-mail cweber{at}ukaachen.de
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-1
, 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.
The complex role of chemokines in the recruitment of mononuclear cells to vascular lesions strongly suggests their specialization and cooperation in the atherosclerotic disease process. This review highlights recent insights into the function of chemokines in mediating distinct steps during the recruitment of monocytes and T cells to native atherosclerotic and neointimal lesions.
Key Words: atherosclerosis • chemokines • leukocytes • receptors
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