Oxidized LDL-induced injury and apoptosis in atherosclerosis. Potential roles for oxysterols.
The cell injury caused by oxidized lipoproteins was among the first findings that led to the theory that it is the oxidation of low-density lipoprotein (LDL), not just LDL concentration, that leads to arterial disease. Voluminous studies have now revealed that oxidized lipoproteins and their constituents can induce numerous effects on cells that can be construed to be atherogenic. Cell injury is but one of these, and it is these injurious effects that are the focus of this brief review. Cell injury and death appear to play multiple roles in lesion development and the toxic lipid constituents of oxidized lipoproteins, including a variety of oxysterols, are candidates for the in vivo effectors of this cytotoxicity. Recent studies have focused on the mechanisms of oxidized lipoprotein-induced cell death, whether the cells die by apoptosis or necrosis, and the identities of the toxins that induce injury. Understanding the roles of these agents in lesion development could lead to therapies that modulate cell death and inhibit lesion formation.
Colles
S M
SM
Departments of Biomedical Engineering and Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Maxson
J M
JM
Carlson
S G
SG
Chisolm
G M
GM
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001161:Arteriosclerosis / Q000209:etiology* / Q000503:physiopathology*; D005218:Fat Necrosis / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008077:Lipoproteins, LDL / Q000009:adverse effects* / Q000378:metabolism*; D011987:Receptors, Steroid / Q000187:drug effects / Q000502:physiology*; D000098825:Oxysterol Binding Proteins
D000975:Antioxidants; D008077:Lipoproteins, LDL; D011987:Receptors, Steroid; C099252:oxidized low density lipoprotein; D000098825:Oxysterol Binding Proteins