The vicious circle between oxidative stress and inflammation in atherosclerosis.
The initial event in atherogenesis is the increased transcytosis of low density lipoprotein, and its subsequent deposition, retention and modification in the subendothelium. It is followed by the infiltration of activated inflammatory cells from the coronary circulation into the arterial wall. There they secrete reactive oxygen species (ROS) and produce oxidized lipoproteins capable of inducing endothelial cell apoptosis, and thereby plaque erosion. Activated T lymphocytes, macrophages and mast cells, accumulate in the eroded plaque where they secrete a variety of proteases capable of inducing degradation of extracellular proteins, thereby rendering the plaques more prone to rupture. This review summarizes the recent advancements in the understanding of the roles of ROS and oxidized lipoproteins in the activation of inflammatory cells and inducing signalling pathways related to cell death and apoptosis. In addition, it presents evidence that this vicious circle between oxidative stress and inflammation does not only occur in the diseased arterial wall, but also in adipose tissues. There, oxidative stress and inflammation impair adipocyte maturation resulting in defective insulin action and adipocytokine signalling. The latter is associated with increased infiltration of inflammatory cells, loss of anti-oxidant protection and cell death in the arterial wall.
Hulsmans
Maarten
M
Atherosclerosis and Metabolism Unit, Department of Cardiovascular Diseases, Katholieke Universiteit Leuven, Belgium.
Holvoet
Paul
P
D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D050197:Atherosclerosis / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology; D008074:Lipoproteins / Q000737:chemistry / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D008074:Lipoproteins; D017382:Reactive Oxygen Species