Neutrophils, hypercholesterolemia, and atherogenesis.

A critical role for hypercholesterolemia in the pathogenesis of atherosclerosis is firmly established. However, we still have much to learn about how hypercholesterolemia leads to the development of atherosclerotic heart disease and the spectrum of cellular participants involved. Atherosclerosis is viewed as a chronic inflammatory process, with our focus of attention dwelling on the role of cells recognized within the artery wall, including endothelial cells, monocytederived cells, and T lymphocytes.1–3 Hypercholesterolemiainduced activation of each of these cells has been mechanistically linked to multiple early processes in atherosclerosis, including upregulation of key adhesion proteins, chemokines, and cytokines that cumulatively orchestrate inflammatory cell trafficking into the vessel wall.4 A critical role for neutrophils, however, in the early atherosclerotic process has been conspicuously absent from the mainstream line of thought, no doubt because neutrophils are rarely observed in early atherosclerotic plaque compared with other inflammatory cell types.