Immune and Inflammatory Mechanisms of Atherosclerosis (*)

Annu Rev Immunol. 2009;27:165-97. doi: 10.1146/annurev.immunol.021908.132620.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Arteries / immunology*
  • Arteries / metabolism
  • Atherosclerosis / immunology*
  • Atherosclerosis / metabolism
  • Cell Adhesion Molecules / immunology
  • Cell Adhesion Molecules / metabolism
  • Cholesterol, LDL / immunology
  • Cholesterol, LDL / metabolism
  • Cytokines / immunology
  • Cytokines / metabolism
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Glycation End Products, Advanced / immunology
  • Glycation End Products, Advanced / metabolism
  • Humans
  • Inflammation / immunology*
  • Inflammation / metabolism
  • Inflammation Mediators / immunology*
  • Inflammation Mediators / metabolism
  • Leukocytes / immunology*
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mast Cells / immunology
  • Mast Cells / metabolism
  • Nitric Oxide / immunology
  • Nitric Oxide / metabolism

Substances

  • Cell Adhesion Molecules
  • Cholesterol, LDL
  • Cytokines
  • Glycation End Products, Advanced
  • Inflammation Mediators
  • Nitric Oxide