β2-glycoprotein I and oxidative inflammation in early atherogenesis: A progression from innate to adaptive immunity?

The innate immune system represents the first line of host defense against a wide variety of pathogens and endogenous danger signals. It relies on trans-membrane signaling and cytoplasmic receptors (danger sensors) to trigger early inflammatory responses. As with the adaptive immunity, an innate immune response can cause tissue injury, chronic inflammation and disease. Nucleotide-binding leucine-rich proteins (NLRs) are a family of cytoplasmic receptors for endogenous danger signals. Inflammasomes are multi-molecular complexes of pyrin-containing NLRs (NLRPs) that regulate pro-inflammatory caspases and interleukin 1 cytokines in response to various stimuli. Cholesterol crystals and oxidation-specific epitopes (oxLDL, ROS) are some of the endogenous signals capable of activating NLRP inflammasomes. Thus, an inflammasome-induced IL-1 beta dysregulation may represent an early atherogenic mechanism that initiates atherosclerosis. The plasma protein, beta 2-glycoprotein I (beta 2GPI), complexed to anionic phospholipids is the main antigenic target for antiphospholipid antibodies. In addition to anticoagulant properties, circulating beta 2GPI has more pleiotropic functions affecting fibrinolysis, angiogenesis, apoptosis and atherogenesis. OxLDL interacts with beta 2GPI to form oxLDL/beta 2GPI pro-atherogenic complexes in both autoimmune-mediated and non-autoimmune atherothrombotic diseases. Due to its interaction with oxLDL, the contribution and implication of beta 2GPI in early atherogenesis via the innate (inflammasome/IL-1) system are hypothesized. (C) 2012 Elsevier B.V. All rights reserved.