Immune and Inflammatory Mechanisms of Atherosclerosis

Abstract

Atherosclerosis is an inflammatory disease of the wall of large-and medium-sized arteries that is precipitated by elevated levels of low-density lipoprotein (LDL) cholesterol in the blood. Although dendritic cells (DCs) and lymphocytes are found in the adventitia of normal arteries, their number is greatly expanded and their distribution changed in human and mouse atherosclerotic arteries. Macrophages, DCs, foam cells, lymphocytes, and other inflammatory cells are found in the intimal atherosclerotic lesions. Beneath these lesions, adventitial leukocytes organize in clusters that resemble tertiary lymphoid tissues. Experimental interventions can reduce the number of available blood monocytes, from which macrophages and most DCs and foam cells are derived, and reduce atherosclerotic lesion burden without altering blood lipids. Under proatherogenic conditions, nitric oxide production from endothelial cells is reduced and the burden of reactive oxygen species (ROS) and advanced glycation end products (AGE) is increased. Incapacitating ROS-generating NADPH oxidase or the receptor for AGE (RAGE) has beneficial effects. Targeting inflammatory adhesion molecules also reduces atherosclerosis. Conversely, removing or blocking IL-10 or TGF-β accelerates atherosclerosis. Regulatory T cells and B1 cells secreting natural antibodies are atheroprotective. This review summarizes our current understanding of inflammatory and immune mechanisms in atherosclerosis.

Smad6-specific recruitment of Smurf E3 ligases mediates TGF-β1-induced degradation of MyD88 in TLR4 signalling

“…Prolonged or excessive inflammation may cause the accumulation of a variety of cellular injuries such as DNA damage, eventually resulting in inflammation-related diseases such as cancer, atherosclerosis and obesity [35][36][37][38] .…”

Chlamydophila pneumoniae phospholipase D (CpPLD) drives Th17 inflammation in human atherosclerosis

“…The involvement of the TLR4 receptor in the activation of monocytes by CpPLD was further supported by the abrogation of CpPLDinduced IL-23 expression by a specific anti-TLR4 blocking antibody. Current evidence indicates that CCL-4, CCL-2, CCL-20, CXCL-9, VCAM-1, and ICAM-1 are important in the genesis of atherosclerosis (30) and that CCL2 and CCL20 are relevant in promoting Th17 cell migration (31)(32)(33). We have investigated the potential role of CpPLD on the expression of different molecules by EC.…”

“…Patients (Cp-pos) were selected on the basis of detectable serum levels of anti-C. pneumoniae antibodies (Eurospital). Fresh plaque-derived T cells (1 × 10 5 ) were stimulated by immobilized anti-CD3 (OKT3) monoclonal antibody (5 μg/mL) in round-bottom microwell plates (30). After 72 h of stimulation, supernatants were collected and assayed for IL-17 and IL-21 by ELISA (R&D Systems and eBioscience, respectively).…”

Endothelial Dysfunction in Tristetraprolin-deficient Mice Is Not Caused by Enhanced Tumor Necrosis Factor-α Expression

“…Today the key role of inflammation during atherogenesis is well accepted (5). Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with enhanced cardiovascular mortality (6 -8).…”