(Circulation. 2001;103:1509.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Molecular Fingerprint of Interferon-
Signaling in Unstable Angina
From the Department of Medicine, Mayo Clinic and Foundation, Rochester, Minn.
Correspondence to C.M. Weyand, MD, Mayo Clinic, 200 First St SW, Rochester, MN 55905. E-mail weyand.cornelia{at}mayo.edu
Background—Activation
of circulating monocytes in patients with acute coronary
syndromes may reflect exposure to bacterial products or stimulation
by cytokines such as IFN-
. IFN- 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- driven,
patients with unstable (UA) or stable angina (SA) were compared for
nuclear translocation of STAT-1 complexes and upregulation of
IFN-–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- 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- signaling in vivo.
Conclusions—Monocytes
from UA patients exhibit a molecular fingerprint of recent IFN-
triggering, such as nuclear translocation of STAT-1 complexes and
upregulation of IFN-–inducible genes CD64 and IP-10, which suggests
that monocytes are activated, at least in part, by IFN-.
IFN- may derive from stimulated T lymphocytes, which implicates
specific immune responses in the pathogenesis of acute coronary
syndromes.
Key Words: plaque • coronary disease • lymphocytes • immune system • inflammation
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