Patrizia Ferroni, Stefania Basili and Giovanni Davi Pages 157 - 169 ( 13 )
Atherogenic cofactors, such as altered cholesterol metabolism, may impact locally on inflammatory responses in atherosclerotic lesions. Blood levels of inflammatory markers (e.g., C-reactive protein, fibrinogen) have been associated with hypercholesterolemia and with overt atherothrombotic disorders. More recently, cytokines (e.g., interleukin-6, interleukin-1β) and soluble adhesion molecules (e.g., selectins, intercellular adhesion molecule-1, vascular cell adhesion molecule-1) have been associated with both hypercholesterolemia and atherosclerotic disease, suggesting their use as potential therapeutic targets for the non-specific “anti-inflammatory” treatment of atherosclerosis. The inflammatory response associated with hypercholesterolemia involves not only the intrinsic cells of the artery wall, but also circulating cells. Platelets participate in this disease process through the release of a wide variety of biologically active substances. An imbalance of the hemostatic system and persistent in vivo platelet activation can be observed in hypercholesterolemia and may have pathophysiological implications in the development and progression of atherosclerotic plaques. Recent findings on the inflammatory actions of platelets have esta blished the potential for a pr eviously unr ecognize d biologic role for plate le ts in inflammation a nd va scula r injury, and have opened new perspectives in the comprehension of the pathogenetic mechanism(s) of atherosclerosis. Stimulated platele ts ac tively synthesize proinflammatory cytokines ( e.g., CD40L, IL-1 β) and are able to r ele ase c he mokines (i.e., platelet factor-4, RANT ES) which have been all involved in the inflammatory process associated with hyper cholesterole mia . This review will summarize the present understanding of the interplay between hypercholesterolemia, inflammation and platelet activation in the development and progression of atherosclerosis, and we also discuss the effects of lipid-lowering treatment on these phenomena.
hypercholesterolemia, inflammation, prothrombotic state, platelet activation, thrombin generation, c-reactive protein, cytokines, chemokines
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