Atherosclerosis: cell biology and lipoproteinsOxidized low density lipoprotein and innate immune receptorsMiller, Yury I.; Chang, Mi-Kyung; Binder, Christoph J.; Shaw, Peter X.; Witztum, Joseph L.Author Information Department of Medicine, University of California, San Diego, La Jolla, California, USA Correspondence to Yury I. Miller or Joseph L. Witztum, University of California, San Diego, 1080 Basic Science Building, 9500 Gilman Drive, La Jolla, CA 92093-0682, USA Tel: +1 858 534 4347; fax: +1 858 534 2005; e-mail: firstname.lastname@example.org or email@example.com Current Opinion in Lipidology: October 2003 - Volume 14 - Issue 5 - p 437-445 Buy Abstract Purpose of review 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. Recent findings 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 Fcγ 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. Summary 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. © 2003 Lippincott Williams & Wilkins, Inc.