TLR signaling and trapped vascular dendritic cells in the development of atherosclerosis

The Framingham Heart Study established a link between serum lipoproteins and atherosclerosis but a crucially important feature of the disease has been neglected: it is primarily an immunological disorder. Here, we reframe atherosclerosis in terms of recent progress in understanding the immunological mechanisms underlying the disorder, and advance a new conceptual model for the future. We place vascular dendritic cells squarely at the forefront, and propose that a sentinel network of vascular dendritic cells (DCs) sample and process exogenous and endogenous antigens that can trigger an inflammatory nidus within the arterial wall. Our model postulates that two components are essential to the development of atheromata: vascular DCs and intact myeloid differentiation (MyD)88-dependent signaling by Toll-like receptors.