Circulating activated platelets exacerbate atherosclerosis in mice deficient in apolipoprotein E

Yuqing Huo, Andreas Schober, S. Bradley Forlow, David F. Smith, Matthew Craig Hyman, Steffen Jung, Dan R. Littman, Christian Weber, Klaus Ley

Research output: Contribution to journalArticle

777 Scopus citations

Abstract

We studied whether circulating activated platelets and platelet-leukocyte aggregates cause the development of atherosclerotic lesions in apolipoprotein-E-deficient (Apoe-/-) mice. Circulating activated platelets bound to leukocytes, preferentially monocytes, to form platelet-monocyte/leukocyte aggregates. Activated platelets and platelet-leukocyte aggregates interacted with atherosclerotic lesions. The interactions of activated platelets with monocytes and atherosclerotic arteries led to delivery of the platelet-derived chemokines CCL5 (regulated on activation, normal T cell expressed and secreted, RANTES) and CXCL4 (platelet factor 4) to the monocyte surface and endothelium of atherosclerotic arteries. The presence of activated platelets promoted leukocyte binding of vascular cell adhesion molecule-1 (VCAM-1) and increased their adhesiveness to inflamed or atherosclerotic endothelium. Injection of activated wild-type, but not P-selectin-deficient, platelets increased monocyte arrest on the surface of atherosclerotic lesions and the size of atherosclerotic lesions in Apoe-/- mice. Our results indicate that circulating activated platelets and platelet-leukocyte/monocyte aggregates promote formation of atherosclerotic lesions. This role of activated platelets in atherosclerosis is attributed to platelet P-selectin-mediated delivery of platelet-derived proinflammatory factors to monocytes/leukocytes and the vessel wall.

Original languageEnglish (US)
Pages (from-to)61-67
Number of pages7
JournalNature Medicine
Volume9
Issue number1
DOIs
StatePublished - Jan 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Huo, Y., Schober, A., Forlow, S. B., Smith, D. F., Hyman, M. C., Jung, S., Littman, D. R., Weber, C., & Ley, K. (2003). Circulating activated platelets exacerbate atherosclerosis in mice deficient in apolipoprotein E. Nature Medicine, 9(1), 61-67. https://doi.org/10.1038/nm810