BACKGROUND Rupture of atherosclerotic plaques is probably the most important mechanism underlying the sudden onset of acute coronary syndromes. Macrophages may release lytic enzymes that degrade the fibrous cap and therefore produce rupture of the atherosclerotic plaque. This study was designed to quantify macrophage content in coronary plaque tissue from patients with stable and unstable coronary syndromes. METHODS AND RESULTS Hematoxylin and eosin and immunostaining with anti-human macrophage monoclonal antibody (PG-M1) were performed. Computerized planimetry was used to analyze 26 atherectomy specimens comprising 524 pieces of tissue from 8 patients with chronic stable angina, 8 patients with unstable angina, and 10 patients with non-Q-wave myocardial infarction. Total plaque area was 417 +/- 87 mm2 x 10(-2) in patients with stable angina, 601 +/- 157 mm2 x 10(-2) in patients with unstable angina, and 499 +/- 87 mm2 x 10(-2) in patients with non-Q-wave myocardial infarction (P = NS). The macrophage-rich area was larger in plaques from patients with unstable angina (61 +/- 18 mm2 x 10(-2)) and non-Q-wave myocardial infarction (87 +/- 32 mm2 x 10(-2)) than in plaques from patients with stable angina (14 +/- 5 mm2 x 10(-2)) (P = .024). The percentage of the total plaque area occupied by macrophages was also larger in patients with unstable angina (13.3 +/- 5.6%) and non-Q-wave myocardial infarction (14.6 +/- 4.6%) than in patients with stable angina (3.14 +/- 1%) (P = .018). Macrophage-rich sclerotic tissue was largest in patients with non-Q-wave myocardial infarction (67 +/- 30 mm2 x 10(-2)) and unstable angina (55 +/- 19 mm2 x 10(-2)) than in patients with stable angina (11.5 +/- 4.1 mm2 x 10(-2)) (P = .046). Macrophage-rich atheromatous gruel was also largest in patients with non-Q-wave myocardial infarction (15 +/- 4 mm2 x 10(-2)) than in patients with unstable angina (3.3 +/- 1.7 mm2 x 10(-2)) or stable angina (2.4 +/- 1.2 mm2 x 10(-2)) (P = .026). CONCLUSIONS Macrophage-rich areas are more frequently found in patients with unstable angina and non-Q-wave myocardial infarction. This suggests that macrophages are a marker of unstable atherosclerotic plaques and may play a significant role in the pathophysiology of acute coronary syndromes.

Arterial thrombosis is considered to arise from the interaction of tissue factor (TF) in the vascular wall with platelets and coagulation factors in circulating blood. According to this paradigm, coagulation is initiated after a vessel is damaged and blood is exposed to vessel-wall TF. We have examined thrombus formation on pig arterial media (which contains no stainable TF) and on collagen-coated glass slides (which are devoid of TF) exposed to flowing native human blood. In both systems the thrombi that formed during a 5-min perfusion stained intensely for TF, much of which was not associated with cells. Antibodies against TF caused ≈70% reduction in the amount of thrombus formed on the pig arterial media and also reduced thrombi on the collagen-coated glass slides. TF deposited on the slides was active, as there was abundant fibrin in the thrombi. Factor VII _ai , a potent inhibitor of TF, essentially abolished fibrin production and markedly reduced the mass of the thrombi. Immunoelectron microscopy revealed TF-positive membrane vesicles that we frequently observed in large clusters near the surface of platelets. TF, measured by factor X _a formation, was extracted from whole blood and plasma of healthy subjects. By using immunostaining, TF-containing neutrophils and monocytes were identified in peripheral blood; our data raise the possibility that leukocytes are the main source of blood TF. We suggest that blood-borne TF is inherently thrombogenic and may be involved in thrombus propagation at the site of vascular injury.

Background The thrombogenicity of a disrupted atherosclerotic lesion is dependent on the nature and extent of the plaque components exposed to flowing blood together with local rheology and a variety of systemic factors. We previously reported on the different thrombogenicity of the various types of human atherosclerotic lesions when exposed to flowing blood in a well-characterized perfusion system. This study examines the role of tissue factor in the thrombogenicity of different types of atherosclerotic plaques and their components. Methods and Results Fifty human arterial segments (5 foam cell–rich, 9 collagen-rich, and 10 lipid-rich atherosclerotic lesions and 26 normal, nonatherosclerotic segments) were exposed to heparinized blood at high shear rate conditions in the Badimon perfusion chamber. The thrombogenicity of the arterial specimens was assessed by ¹¹¹ In-labeled platelets. After perfusion, specimens were stained for tissue factor by use of an in situ binding assay for factor VIIa. Tissue factor in specimens was semiquantitatively assessed on a scale of 0 to 3. Platelet deposition on the lipid-rich atheromatous core was significantly higher than on all other substrates ( P =.0002). The lipid-rich core also exhibited the most intense tissue factor staining (3±0.1 arbitrary units) compared with other arterial components. Comparison of all specimens showed a positive correlation between quantitative platelet deposition and tissue factor staining score ( r =.35, P <.01). Conclusions Our results show that tissue factor is present in lipid-rich human atherosclerotic plaques and suggest that it is an important determinant of the thrombogenicity of human atherosclerotic lesions after spontaneous or mechanical plaque disruption.

Background —High-resolution MRI has the potential to noninvasively image the human coronary artery wall and define the degree and nature of coronary artery disease. Coronary artery imaging by MR has been limited by artifacts related to blood flow and motion and by low spatial resolution. Methods and Results —We used a noninvasive black-blood (BB) MRI (BB-MR) method, free of motion and blood-flow artifacts, for high-resolution (down to 0.46 mm in-plane resolution and 3-mm slice thickness) imaging of the coronary artery lumen and wall. In vivo BB-MR of both normal and atherosclerotic human coronary arteries was performed in 13 subjects: 8 normal subjects and 5 patients with coronary artery disease. The average coronary wall thickness for each cross-sectional image was 0.75±0.17 mm (range, 0.55 to 1.0 mm) in the normal subjects. MR images of coronary arteries in patients with ≥40% stenosis as assessed by x-ray angiography showed localized wall thickness of 4.38±0.71 mm (range, 3.30 to 5.73 mm). The difference in maximum wall thickness between the normal subjects and patients was statistically significant ( P <0.0001). Conclusions —In vivo high-spatial-resolution BB-MR provides a unique new method to noninvasively image and assess the morphological features of human coronary arteries. This may allow the identification of atherosclerotic disease before it is symptomatic. Further studies are necessary to identify the different plaque components and to assess lesions in asymptomatic patients and their outcomes.

PERCUTANEOUS transluminal angioplasty is frequently used in selected patients to decrease stenoses in atherosclerotic peripheral arteries,^{1 , 2} renal arteries,^{3 4 5 6} and coronary arteries.^{7 8 9} There has been much controversy over the mechanism of successful transluminal angioplasty. It was initially postulated that enlargement of the vascular lumen was due to compression of atheromatous plaque.² However, experiments in animals and autopsy studies in human beings^{10 11 12 13 14 15 16 17} have shown that transluminal angioplasty produces endothelial desquamation and splitting of the atheromatous plaque. Attempts to extrapolate these findings to the mechanism of clinically successful angioplasty have been subjected to the criticism that post-mortem tissue and animal models of atherosclerosis . . .