The combined role of P- and E-selectins in atherosclerosis

Zhao Ming Dong, Susan M. Chapman, Allison A. Brown, Paul S. Frenette, Richard O. Hynes, Denisa D. Wagner

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343 Scopus citations

Abstract

P- and E-selectins are adhesion molecules mediating the first step in leukocyte extravasation. Because their function in leukocyte adhesion is overlapping, we hypothesized that there might be a combined effect of these selectins on the development of atherosclerotic lesions. We bred P- and E- selectin-double-deficient mice onto the low-density lipoprotein receptor (LDLR)-deficient background (LDLR-/- P/E-/-) and compared lesion development in these mice to that in mice wild type for both selectins (LDLR-/- P/E+/+). After 8 wk on atherogenic diet, the LDLR-/- P/E-/- mice developed fatty streaks in the aortic sinus that were five times smaller than those in LDLR- /- P/E+/+ mice. The density of macrophages in the fatty streaks was comparable between LDLR-/- P/E+/+ and LDLR-/- P/E-/- mice. After 22 wk on the diet, the lesions spread throughout the aorta but this process was delayed in LDLR-/- P/E-/- mice. At 37 wk on diet, the lesions progressed to the fibrous plaque stage in both genotypes. However, the lesions in the aortic sinus in LDLR-/- P/E-/- mice were 40% smaller and less calcified than those of LDLR- /- P/E+/+ mice. Our results suggest that P- and E-selectins together play an important role in both early and advanced stages of atherosclerotic lesion development.

Original languageEnglish (US)
Pages (from-to)145-152
Number of pages8
JournalJournal of Clinical Investigation
Volume102
Issue number1
DOIs
StatePublished - Jul 1 1998
Externally publishedYes

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Keywords

  • Animal model for atherosclerosis
  • Leukocyte adhesion
  • Lipofuscin
  • Macrophage
  • Smooth muscle cells

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Dong, Z. M., Chapman, S. M., Brown, A. A., Frenette, P. S., Hynes, R. O., & Wagner, D. D. (1998). The combined role of P- and E-selectins in atherosclerosis. Journal of Clinical Investigation, 102(1), 145-152. https://doi.org/10.1172/JCI3001