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 language | English (US) |
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Pages (from-to) | 1509-1514 |
Number of pages | 6 |
Journal | Circulation |
Volume | 103 |
Issue number | 11 |
DOIs | |
State | Published - Mar 20 2001 |
Keywords
- Coronary disease
- Immune system
- Inflammation
- Lymphocytes
- Plaque
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)