Arterial macrophages and regenerating endothelial cells express P-selectin in atherosclerosis-prone apolipoprotein E-deficient mice

Guohong Li, John M. Sanders, Elizabeth T. Phan, Klaus Ley, Ian J. Sarembock

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

P-selectin expression has been reported in platelets, endothelial cells, and vascular smooth muscle cells in response to vascular injury. Here, we report P-selectin expression on macrophages in the arterial wall after carotid denudation injury and spontaneous atherosclerosis in atherosclerosis-prone apoE-deficient (apoE-/-) mice. Double-immunofluorescence staining revealed robust P-selectin expression in macrophage-rich regions of both denudation-induced carotid neointimal lesions and innominate atherosclerotic plaques. Co-localization of P-selectin with macrophages was verified at the single cell level using double immunostaining plus 4,6-diamidino-2-phenylindole (for nuclei) counter-staining. No platelet staining was seen in association with the macrophage staining, excluding platelet contamination. Furthermore, P-selectin mRNA expression was readily detectable in macrophage-rich plaques of atherosclerotic innominate arteries and blood monocyte-derived macrophages from apoE-/- mice. Strong P-selectin expression was also seen in the areas of regenerated endothelium after arterial injury. In addition, co-localization of P-selectin with vascular smooth muscle cells was readily observed in denudation-injured carotid arteries at 7 and 14 days. We conclude that macrophages in carotid injury-induced neointimal lesions and spontaneous atherosclerotic plaques of the innominate artery acquire the ability to express P-selectin, as does regenerating endothelium. These findings provide a potential new paradigm in macrophage-mediated vascular inflammation, atherosclerosis, and neointimal hyperplasia after arterial injury.

Original languageEnglish (US)
Pages (from-to)1511-1518
Number of pages8
JournalAmerican Journal of Pathology
Volume167
Issue number6
DOIs
StatePublished - Dec 2005

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

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