Cholesterol, Inflammasomes, and Atherogenesis
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LIPIDS (JM ORDOVAS, SECTION EDITOR)
Cholesterol, Inflammasomes, and Atherogenesis Jose M. Ordovas-Montanes & Jose M. Ordovas
Published online: 29 November 2011 # Springer Science+Business Media, LLC 2011
Abstract Plasma cholesterol levels have been strongly associated with atherogenesis, underscoring the role of lipid metabolism in defining cardiovascular disease risk. However, the atherosclerotic plaque is highly dynamic and contains elements of both the innate and adaptive immune system that respond to the aberrant accumulation of lipids in the subendothelial space. Previous research has focused on defining how proinflammatory cytokines synthesized by macrophages, such as interleukin-1β (IL-1β), modulate the progression of atherosclerosis, supporting the notion that chronic inflammation accelerates atherogenesis. More recently, emphasis has been placed on the elucidation of the mechanisms that contribute to pro–IL-1β production and finally its processing via multiprotein complexes termed the inflammasomes, a family of cytosolic multiprotein complexes that serve as sensors of either pathogen invasion or cellular stress (ie, cholesterol crystals) and work via J. M. Ordovas-Montanes Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, New Research Building, Rm 836, Boston, MA 02115, USA J. M. Ordovas (*) Nutrition and Genomics Laboratory, USDA, HNRCA at Tufts University, 711 Washington St., Boston, MA 02111, USA e-mail: [email protected] J. M. Ordovas The Department of Epidemiology and Population Genetics, Centro Nacional Investigación Cardiovasculares Madrid, Madrid, Spain J. M. Ordovas IMDEA Alimentacion, Madrid, Spain
triggering caspase-1–mediated processing of pro–IL-1β to IL-1β. Based on this link between cholesterol metabolism, NLRP3 inflammasome activation, and IL-1β release, it is important to re-evaluate how the atherogenic environment stimulates immune cells to produce IL-1β. Keywords Inflammasome . Inflammation . Cholesterol . Atherogenesis . Cardiovascular diseases
Introduction Lipid metabolism and atherosclerosis have been intimately linked and studied for many decades. However, the atherosclerotic plaque is by no means just a static accumulation of lipids [1]; instead, it contains elements of both the innate and adaptive immune system that respond to the aberrant accumulation of lipids in the arterial wall [2]. Of these cells, blood monocytes, which differentiate into macrophages when they enter the plaque, have been shown to play a key role in plaque progression [3]. Due to this recognition by researchers, the mechanistic understanding of atherosclerotic plaque progression has increased dramatically in the past decade. Much of this research has focused on defining how proinflammatory cytokines synthesized by macrophages, such as interleukin 1-β (IL-1β), modulate the progression of atherosclerosis, with the basic conclusion that inflammatory markers such as IL-1β accelerate atherogenesis. Despite all of this research, the mechanistic factors linking ab
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