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PMID: 19302038 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Immune and inflammatory mechanisms of atherosclerosis (*).

Annual review of immunology ·Vol. 27 ·2009-00-00 ·Pages 165-97

Galkina E, Ley K

Abstract

Atherosclerosis is an inflammatory disease of the wall of large- and medium-sized arteries that is precipitated by elevated levels of low-density lipoprotein (LDL) cholesterol in the blood. Although dendritic cells (DCs) and lymphocytes are found in the adventitia of normal arteries, their number is greatly expanded and their distribution changed in human and mouse atherosclerotic arteries. Macrophages, DCs, foam cells, lymphocytes, and other inflammatory cells are found in the intimal atherosclerotic lesions. Beneath these lesions, adventitial leukocytes organize in clusters that resemble tertiary lymphoid tissues. Experimental interventions can reduce the number of available blood monocytes, from which macrophages and most DCs and foam cells are derived, and reduce atherosclerotic lesion burden without altering blood lipids. Under proatherogenic conditions, nitric oxide production from endothelial cells is reduced and the burden of reactive oxygen species (ROS) and advanced glycation end products (AGE) is increased. Incapacitating ROS-generating NADPH oxidase or the receptor for AGE (RAGE) has beneficial effects. Targeting inflammatory adhesion molecules also reduces atherosclerosis. Conversely, removing or blocking IL-10 or TGF-beta accelerates atherosclerosis. Regulatory T cells and B1 cells secreting natural antibodies are atheroprotective. This review summarizes our current understanding of inflammatory and immune mechanisms in atherosclerosis.

MeSH Terms
Animals Arteries/immunology,metabolism Atherosclerosis/immunology,metabolism Cell Adhesion Molecules/immunology,metabolism Cholesterol, LDL/immunology,metabolism Cytokines/immunology,metabolism Dendritic Cells/immunology,metabolism Glycation End Products, Advanced/immunology,metabolism Humans Inflammation/immunology,metabolism Inflammation Mediators/immunology,metabolism Leukocytes/immunology Macrophages/immunology,metabolism Mast Cells/immunology,metabolism Nitric Oxide/immunology,metabolism
Chemicals
Cell Adhesion Molecules Cholesterol, LDL Cytokines Glycation End Products, Advanced Inflammation Mediators Nitric Oxide
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Galkina Elena
Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, Virginia 23507-1696, USA. galkinev@evms.edu
Ley Klaus
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Article Info
Journal
Annual review of immunology
Abbr.
Annu Rev Immunol
ISSN
0732-0582
DOI
10.1146/annurev.immunol.021908.132620
Email
galkinev@evms.edu
Published
2009-00-00
Pages
165-97
Language
English
Region
United States
NLM ID
8309206
PMCID
PMC2734407
Subset
IM
Grants
NHLBI NIH HHS · R01 HL058108-05 · United States
NHLBI NIH HHS · P01 HL055798-110009 · United States
NHLBI NIH HHS · HL 58108 · United States
NHLBI NIH HHS · P01 HL055798 · United States
NHLBI NIH HHS · R01 HL058108-04 · United States
NHLBI NIH HHS · HL 55798 · United States
NHLBI NIH HHS · R01 HL058108 · United States
External Links
PubMed source DOI: 10.1146/annurev.immunol.021908.132620 PMC Full Text View journal details
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