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Atherogenesis in perspective: Hypercholesterolemia and inflammation as partners in crime

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A historical perspective on atherosclerosis allows us to reflect on the once controversial hypotheses in the field. Plaque formation was once thought to be dependent upon hypercholesterolemia alone, or solely in response to injury. More recently, inflammatory cascades were thought to be at the root of lesion development. A more realistic view may be that atherosclerosis is neither exclusively an inflammatory disease nor solely a lipid disorder: it is both.

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Figure 1: Illustration of the structure of a low-density lipoprotein (LDL) particle.

JOHN BAVOSI / SCIENCE PHOTO LIBRARY / PHOTO RESEARCHERS, INC.

Figure 2: The consensus linear sequence of events generating the fatty streak lesion.

D. Maizels

Figure 3: Native LDL cannot induce foam-cell formation because uptake is slow and because its receptor downregulates.

D. Maizels

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Steinberg, D. Atherogenesis in perspective: Hypercholesterolemia and inflammation as partners in crime. Nat Med 8, 1211–1217 (2002). https://doi.org/10.1038/nm1102-1211

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