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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:E16.)
© 2007 American Heart Association, Inc.

Letters to the Editor

Letter to the Editor

Decreased Atherosclerosis in Mice Deficient in Tumor Necrosis Factor- Receptor-II (p75)

Unni M. Chandrasekharan; Lori Mavrakis; Jonathan D. Smith; Paul E. DiCorleto

Department of Cell Biology, Lerner Research Institute and Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio

Tracy L. Bonfield

Department of Pulmonary Medicine, Lerner Research Institute and Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio

An extract of the first 250 words of the full text is provided, because this article has no abstract.

To the Editor:

TNF- induces a wide variety of proatherogenic molecules,¹ and inhibition of TNF- in apoe^–/– mice results in diminished atherosclerosis suggesting the involvement of TNF- in atherogenesis.^2,3 TNF- elicits its effects by activating 2 cell-surface receptors, namely p55 and p75. Earlier, Blessing et al reported that apoe^–/– mice lacking p55 fed a chow diet did not show altered lesion progression or plaque composition.⁴ Recently, we showed that p75 is required for TNF-–induced leukocyte–endothelial cell interaction and inflammation in vivo.⁵ Because inflammation plays an integral role in atherogenesis, we tested whether the proatherogenic activity of TNF- was mediated by p75. We determined the role of p75 in atherogenesis using apoe^–/– mice lacking p75 receptor. We generated p75^–/–:apoe^–/–, p75^+/–:apoe^–/–, and p75^+/+:apoe^–/– by sister–brother mating of p75^+/–:apoe^–/– parents. Atherosclerotic lesion areas in aortic roots were measured after staining with Oil red O in 16-week-old chow diet-fed female mice. As shown in the Figure, the p75^+/+:apoe^–/– mice had a mean lesion area of 125 000±32 000 µm² (n=10). Lesion area in the hemizygous p75^+/–:apoe^–/– mice was 116 000±48 000 (n=10), which was similar to that in the p75^+/+: apoe^–/– mice, suggesting that one copy of the p75 gene is sufficient to promote its proatherosclerotic effect. The p75^–/–:apoe^–/– mice had a mean lesion area of 72 000±28 000 µm² (n=10), representing a 43% reduction in lesion area compared with the p75^+/+:apoe^–/– mice (P<0.01), and a 37% decrease compared . . . [Full Text of this Article]