Immune and inflammatory mechanisms of atherosclerosis (*).
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.
Galkina
Elena
E
Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, Virginia 23507-1696, USA. galkinev@evms.edu
Ley
Klaus
K
D000818:Animals; D001158:Arteries / Q000276:immunology* / Q000378:metabolism; D050197:Atherosclerosis / Q000276:immunology* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism; D008078:Cholesterol, LDL / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D018836:Inflammation Mediators / Q000276:immunology* / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D009569:Nitric Oxide / Q000276:immunology / Q000378:metabolism
D015815:Cell Adhesion Molecules; D008078:Cholesterol, LDL; D016207:Cytokines; D017127:Glycation End Products, Advanced; D018836:Inflammation Mediators; D009569:Nitric Oxide