The macrophage lipopolysaccharide binding protein gene is an LXR target that promotes macrophage survival and atherosclerosis (original) (raw)

2014, The Journal of Lipid Research

Despite recent advances in our treatment and understanding of its biology, CVD contributes to one in every three deaths (1, 2). Additionally, CVD costs more than any other condition with an estimated annual burden of $312 billion, an astonishing fi gure in light of the growing interest in healthcare utilization and costs (1). This unacceptably high disease burden galvanizes efforts to better understand mechanisms contributing to CVD and developing novel diagnostic and therapeutic strategies. At the epicenter of the most devastating forms of CVD, including myocardial infarction, peripheral vascular disease, and stroke, is atherosclerosis. Atherosclerosis is a chronic condition of the arterial lining characterized by a prolonged asymptomatic phase, making it diffi cult to study in humans. Thus, mouse models have been invaluable in understanding disease mechanisms (3, 4). A hallmark feature of atherosclerosis is the accumulation of cholesterol-loaded macrophages within the vessel wall (5). At the early stages of atherosclerosis, macrophages ingest modifi ed lipoproteins to form "foam cells," and in turn release various substances that recruit smooth muscle cells and other immune cells, ultimately leading to advanced plaque formation (6). Macrophages, as well as other immune cells, have a powerful impact on disease progression (7). Therefore, macrophages are a pivotal cell type in the pathogenesis of atherosclerosis and potential targets for therapy.