Platelet factor 4 mediates vascular smooth muscle cell injury responses

Guanfang Shi, David J. Field, Xiaochun Long, Deanne Mickelsen, Kyung Ae Ko, Sara Ture, Vyacheslav A. Korshunov, Joseph M. Miano, Craig N. Morrell

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Activated platelets release many inflammatory molecules with important roles in accelerating vascular inflammation. Much is known about platelet and platelet-derived mediator interactions with endothelial cells and leukocytes, but few studies have examined the effects of platelets on components of the vascular wall. Vascular smooth muscle cells (VSMCs) undergo phenotypic changes in response to injury including the production of inflammatory molecules, cell proliferation, cell migration, and a decline in the expression of differentiation markers. In this study, we demonstrate that the platelet-derived chemokine platelet factor 4 (PF4/CXCL4) stimulates VSMC injury responses both in vitro and in vivo in a mouse carotid ligation model. PF4 drives a VSMC inflammatory phenotype including a decline in differentiation markers, increased cytokine production, and cell proliferation. We also demonstrate that PF4 effects are mediated, in part, through increased expression of the transcription factor Krüppel-like factor 4. Our data indicate an important mechanistic role for platelets and PF4 in VSMC injury responses both in vitro and in vivo.

Original languageEnglish (US)
Pages (from-to)4417-4427
Number of pages11
JournalBlood
Volume121
Issue number21
DOIs
Publication statusPublished - May 23 2013
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Shi, G., Field, D. J., Long, X., Mickelsen, D., Ko, K. A., Ture, S., ... Morrell, C. N. (2013). Platelet factor 4 mediates vascular smooth muscle cell injury responses. Blood, 121(21), 4417-4427. https://doi.org/10.1182/blood-2012-09-454710