Inflammatory mediators in atherosclerotic vascular disease.
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.
Zernecke
Alma
A
Weber
Christian
C
D000818:Animals; D050197:Atherosclerosis / Q000276:immunology* / Q000517:prevention & control; D018932:Chemokine CCL2 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000097:blood; D054428:Chemokine CX3CL1 / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000378:metabolism; D019742:Chemokines, CC / Q000378:metabolism; D019743:Chemokines, CXC / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000517:prevention & control; D018836:Inflammation Mediators / Q000378:metabolism*; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000276:immunology; D054390:Receptors, CCR2 / Q000378:metabolism; D013234:Stem Cells / Q000276:immunology
D018932:Chemokine CCL2; D018946:Chemokine CCL5; D054428:Chemokine CX3CL1; D054377:Chemokine CXCL12; D019742:Chemokines, CC; D019743:Chemokines, CXC; D018836:Inflammation Mediators; D008263:Macrophage Migration-Inhibitory Factors; D054390:Receptors, CCR2