Oxidized low density lipoprotein and innate immune receptors.
OBJECTIVE
Atherosclerosis is now recognized as a chronic inflammatory disease. This review discusses recent literature reporting that innate immune receptors bind oxidatively modified LDL and its many oxidized moieties and consequently modulate the atherogenic process. These innate pattern recognition receptors are known to play a central role in pro-inflammatory responses to bacteria by binding pathogen-associated molecular patterns. It is hypothesized that oxidized LDL exposes similar molecular patterns recognized by receptors of innate immunity.


RESULTS
Minimally modified LDL and its oxidized phospholipids have been found to bind to CD14 or activate Toll-like receptors on macrophages. In turn, various biological activities have been induced, including the stimulation of cytoskeletal rearrangements that alter phagocytic activity and the stimulation of cytokine secretion, such as IL-8. These findings link modified LDL with innate pattern recognition receptors, such as those involved in the lipopolysaccharide signaling pathway. Human epidemiological studies support the involvement of CD14 and TLR4 in cardiovascular diseases. Oxidized LDL has also been demonstrated to bind to C-reactive protein, an opsonic molecule activating classic complement pathway and Fcgamma receptor endocytosis. These data suggest that C-reactive protein may not only be a strong predictor of clinical disease, but may also play a role in atherogenesis. Recent data on other innate immune receptors are discussed in the context of their potential interactions with oxidized LDL and atherogenesis.


CONCLUSIONS
Recent findings suggest that oxidized forms of LDL interact with innate immune receptors. Further studies are needed to identify the role of these interactions in inflammation and atherosclerosis.
D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D018121:Receptors, Cytokine / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D051116:Receptors, Scavenger; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D018950:Lipopolysaccharide Receptors; D008077:Lipoproteins, LDL; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; C099252:oxidized low density lipoprotein; D002097:C-Reactive Protein