Absence of P-selectin delays fatty streak formation in mice

Robert C. Johnson, Susan M. Chapman, Zhao Ming Dong, Jose M. Ordovas, Tanya N. Mayadas, Joachim Herz, Richard O. Hynes, Ernst J. Schaefer, Denisa D. Wagner

Research output: Contribution to journalArticle

204 Scopus citations

Abstract

P-selectin is expressed on activated endothelium and platelets where it can bind monocytes, neutrophils, stimulated T cells, and platelets. Because recruitment of these cells is critical for atherosclerotic lesion development, we examined whether P-selectin might play a role in atherosclerosis. We intercrossed P-selectin-deficient mice with mice lacking the low density lipoprotein receptor (LDLR) because these mice readily develop atherosclerotic lesions on diets rich in saturated fat and cholesterol. The atherogenic diet stimulated leukocyte rolling in the mesenteric venules of LDLR-deficient mice, and the increase in adhesiveness of the vessels was P-selectin-dependent. Most likely due to the reduced leukocyte interaction with the vessel wall, P-selectin-deficient mice on diet for 8-20 wk formed significantly smaller fatty streaks in the cusp region of the aortae than did P-selectin-positive mice. This difference was more prominent in males. At 37 wk on diet, the lesions in the LDLR-deficient animals progressed to the fibrous plaque stage and were distributed throughout the entire aorta; their size or distribution was no longer dependent on P-selectin. Our results show that P-selectin-mediated adhesion is an important factor in the development of early atherosclerotic lesions, and that adhesion molecules such as P-selectin are involved in the complex process of atherosclerosis.

Original languageEnglish (US)
Pages (from-to)1037-1043
Number of pages7
JournalJournal of Clinical Investigation
Volume99
Issue number5
DOIs
StatePublished - Mar 1 1997

Keywords

  • animal model for atherosclerosis
  • cell adhesion
  • endothelium
  • hypercholesterolemia
  • macrophage

ASJC Scopus subject areas

  • Medicine(all)

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    Johnson, R. C., Chapman, S. M., Dong, Z. M., Ordovas, J. M., Mayadas, T. N., Herz, J., Hynes, R. O., Schaefer, E. J., & Wagner, D. D. (1997). Absence of P-selectin delays fatty streak formation in mice. Journal of Clinical Investigation, 99(5), 1037-1043. https://doi.org/10.1172/JCI119231