The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/2000/1/189/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 1, January 3, 2000 189-194


Brief Definitive Report

P-Selectin or Intercellular Adhesion Molecule (Icam)-1 Deficiency Substantially Protects against Atherosclerosis in Apolipoprotein E–Deficient Mice

Robert G. Collinsa, Rizwan Veljia, Natalia V. Guevarab, M. John Hicksc, Lawrence Chanb,d, and Arthur L. Beaudeta,b

a Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030
b Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030
c Department of Pathology, Baylor College of Medicine, Houston, Texas 77030
d Department of Medicine, Baylor College of Medicine, Houston, Texas 77030
Henry and Emma Meyer Professor and Chair, Dept. of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Rm. T619, Houston, TX 77030.713-798-7773713-798-4795

abeaudet{at}bcm.tmc.edu

The expression of leukocyte and endothelial cell adhesion molecules (CAMs) is essential for the emigration of leukocytes during an inflammatory response. The importance of the inflammatory response in the development of atherosclerosis is indicated by the increased expression of adhesion molecules, proinflammatory cytokines, and growth factors in lesions and lesion-prone areas and by protection in mice deficient in various aspects of the inflammatory response. We have quantitated the effect of deficiency for intercellular adhesion molecule (ICAM)-1, P-selectin, or E-selectin on atherosclerotic lesion formation at 20 wk of age in apolipoprotein (apo) E–/– (deficient) mice fed a normal chow diet. All mice were apo E–/– and CAM+/+ or CAM–/– littermates, and no differences were found in body weight or cholesterol levels among the various genotypes during the study. ICAM-1–/– mice had significantly less lesion area than their ICAM-1+/+ littermates: 4.08 ± 0.70 mm2 for –/– males vs. 5.87 ± 0.66 mm2 for +/+ males, and 3.95 ± 0.65 mm2 for –/– females vs. 5.59 ± 1.131 mm2 for +/+ females, combined P < 0.0001. An even greater reduction in lesion area was observed in P-selectin–/– mice: 3.06 ± 1.04 mm2 for –/– males vs. 5.09 ± 1.22 mm2 for +/+ males, and 2.85 ± 1.26 mm2 for –/– females compared with 5.60 ± 1.19 mm2 for +/+ females, combined P < 0.001. The reduction in lesion area for the E-selectin null mice, although less than that seen for ICAM-1 or P-selectin, was still significant (4.54 ± 2.14 mm2 for –/– males vs. 5.92 ± 0.63 mm2 for +/+ males, and 4.38 ± 0.85 mm2 for –/– females compared with 5.94 ± 1.44 mm2 for +/+ females, combined P < 0.01). These results, coupled with the closely controlled genetics of this study, indicate that reductions in the expression of P-selectin, ICAM-1, or E-selectin provide direct protection from atherosclerotic lesion formation in this model.

Key Words: E-selectin • cell adhesion molecules • aorta • cholesterol • intercellular adhesion molecule-1


© 2000 The Rockefeller University Press


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