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Inflammatory mediators in atherosclerotic vascular disease

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Abstract

An impressive body of work has established the current paradigm of atherosclerosis as an inflammatory process that promotes lesion development and progression. Early atheroma formation is characterized by leukocyte recruitment and expression of inflammatory mediators which is confounded in the context of hyperlipidemia. Evidence for an involvement of both innate and adaptive immunity in lesion formation has emerged, supporting a causal relation between the balance of pro- and anti–inflammatory cytokines and atherogenesis. The function of chemokines in distinct steps during mononuclear cell recruitment to vascular lesions has been studied in genetically deficient mice and other suitable models, and displays a high degree of specialization and cooperation. The contribution of platelet chemokines deposited on endothelium to monocyte arrest, differences in the presentation and involvement of chemokines between native and neointimal lesion formation, and related functions of macrophage migration inhibitory factor, a cytokine with striking structural homology to chemokines are of note. A novel role of chemokines in the recruitment of vascular progenitors during neointimal hyperplasia and in the recovery of endothelial denudation underscores their relevance for atherosclerotic vascular disease. The functional diversity of chemokines in vascular inflammation may potentially allow the selective therapeutic targeting of different atherosclerotic conditions.

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Abbreviations

ApoE:

apolipoprotein E

CCL:

CC chemokine ligand

CCR:

CC chemokine receptor

CD:

cluster of differentiation

CXCL:

CXC chemokine ligand

CXCR:

CXC chemokine receptor

EC:

endothelial cell

GRO:

growth-related oncogene

IFN–γ:

interferon–γ

IL:

interleukin

KC:

keratinocyte–derived chemokine

LDL–R:

low density lipoprotein receptor

MCP:

monocyte chemotactic protein

MIF:

macrophage migration inhibitory factor

Mig/IP10:

monokine induced by IFN–γ/IFN–γ–inducible protein–10

RANTES:

regulated on activation normal T cell expressed and secreted

SDF:

stromal cell–derived factor

SMC:

smooth muscle cell

TGF–β:

transforming growth factor–β

TNF:

tumor necrosis factor

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  1. Kardiovaskuläre Molekularbiologie, Universitätsklinikum Aachen Rheinisch-Westfälische Technische Hochschule Aachen, Pauwelsstr. 30, 52057, Aachen, Germany

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Zernecke, A., Weber, C. Inflammatory mediators in atherosclerotic vascular disease. Basic Res Cardiol 100, 93–101 (2005). https://doi.org/10.1007/s00395-005-0511-6

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