Molecular fingerprint of interferon-γ signaling in unstable angina

Giovanna Liuzzo, Abbe N. Vallejo, Stephen L. Kopecky, Robert L. Frye, David Holmes, Jörg J. Goronzy, Cornelia M. Weyand

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86 Scopus citations

Abstract

Background - Activation of circulating monocytes in patients with acute coronary syndromes may reflect exposure to bacterial products or stimulation by cytokines such as IFN-γ. IFN-γ induces phosphorylation and nuclear translocation of transcription factor STAT-1, which initiates a specific program of gene induction. To explore whether monocyte activation is IFN-γ driven, patients with unstable (UA) or stable angina (SA) were compared for nuclear translocation of STAT-1 complexes and upregulation of IFN-γ-inducible genes CD64 and IP-10. Methods and Results - Peripheral blood mononuclear cells were stained for expression of CD64 on CD14+ monocytes and analyzed by PCR for transcription of IP-10. Expression of CD64 was significantly increased in patients with UA. Monocytes from UA patients remained responsive to IFN-γ in vitro, with accelerated transcriptional competency of CD64. IP-10-specific sequences were spontaneously detectable in 82% of the UA patients and 15% of SA patients (P<0.001). Most importantly, STAT-1 complexes were found in nuclear extracts prepared from freshly isolated monocytes of patients with UA, which provides compelling evidence for IFN-γ signaling in vivo. Conclusions - Monocytes from UA patients exhibit a molecular fingerprint of recent IFN-γ triggering, such as nuclear translocation of STAT-1 complexes and upregulation of IFN-γ-inducible genes CD64 and IP-10, which suggests that monocytes are activated, at least in part, by IFN-γ. IFN-γ may derive from stimulated T lymphocytes, which implicates specific immune responses in the pathogenesis of acute coronary syndromes.

Original languageEnglish (US)
Pages (from-to)1509-1514
Number of pages6
JournalCirculation
Volume103
Issue number11
DOIs
StatePublished - Mar 20 2001

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Keywords

  • Coronary disease
  • Immune system
  • Inflammation
  • Lymphocytes
  • Plaque

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Liuzzo, G., Vallejo, A. N., Kopecky, S. L., Frye, R. L., Holmes, D., Goronzy, J. J., & Weyand, C. M. (2001). Molecular fingerprint of interferon-γ signaling in unstable angina. Circulation, 103(11), 1509-1514. https://doi.org/10.1161/01.CIR.103.11.1509