Circulation, Vol 88, 2493-2500, Copyright © 1993 by American Heart Association
MY Flugelman, R Virmani, R Correa, ZX Yu, A Farb, MB Leon, A Elami, YM Fu, W Casscells and SE Epstein
BACKGROUND. The mechanisms responsible for the transformation of stable
angina to unstable angina, a major cause of morbidity and mortality, are
commonly believed to be plaque rupture and thrombosis. We determined
whether additional mechanisms are operative by analyzing the histopathology
and immuno-histopathology of coronary plaques retrieved by directional
atherectomy of patients with unstable angina in whom no intraluminal
thrombus was demonstrated by angiography. METHODS AND RESULTS. The
histological findings of atherectomy specimens from 34 patients with
unstable angina were compared with those of 24 patients with
postangioplasty restenosis, whose lesions are known to be composed of
smooth muscle cells (SMCs), and 10 patients with stable angina, whose
lesions contain relatively few SMCs. We also studied the expression of
acidic and basic fibroblast growth factors (aFGF and bFGF), whose role in
the vascular response to injury has been established. Specimens from
unstable angina resembled those from postangioplasty restenosis in regard
to SMC abundance (scale, 0 to 3; 1.4 +/- 0.9 versus 1.7 +/- 0.9; P = NS),
and both differed from those of stable angina. Thrombus and/or hemorrhage
occurred in only 34% of patients with unstable angina (compared with 8% of
restenosis patients and in none of stable angina patients). Active lesions
(defined as lesions (defined as lesions containing one or more of the
following: thrombus, hemorrhage, abundant and disorganized SMCs in the
presence of loose connective tissue, or inflammatory infiltrate) were
observed in 56% of the unstable angina patients and in 50% of the
restenosis patients but in none of the stable angina patients. The
expression of aFGF and bFGF was detected in 80% to 100% of unstable angina
(n = 11) and restenosis (n = 10) specimens but in only 1 of 5 stable angina
specimens. CONCLUSIONS. Microscopic evidence of thrombosis and plaque
rupture occurred in only one third of unstable angina patients, selected
because they had no angiographic evidence of intracoronary thrombus.
Moreover, their lesions resembled those of restenosis patients in regard to
SMC abundance, lesion activity, and the expression of aFGF and bFGF. Our
findings therefore suggest that an alternative mechanism to plaque rupture
and thrombus formation may be operative in the precipitation of unstable
angina; namely, in a subset of patients, SMC proliferation may lead to
gradual plaque expansion and thereby to lumenal narrowing and unstable
angina. Our data also suggest a role for aFGF and bFGF in this process.
ARTICLES
Smooth muscle cell abundance and fibroblast growth factors in coronary lesions of patients with nonfatal unstable angina. A clue to the mechanism of transformation from the stable to the unstable clinical state
Cardiology Branch, National Heart, Lung, and Blood Institute, Bethesda, Md 20892.
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