Circulation, Vol 90, 775-778, Copyright © 1994 by American Heart Association
PR Moreno, E Falk, IF Palacios, JB Newell, V Fuster and JT Fallon
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.
ARTICLES
Macrophage infiltration in acute coronary syndromes. Implications for plaque rupture
Cardiovascular Pathology Research Laboratory, Massachusetts General Hospital, Boston.
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H. D. Danenberg, I. Fishbein, J. Gao, J. Monkkonen, R. Reich, I. Gati, E. Moerman, and G. Golomb Macrophage Depletion by Clodronate-Containing Liposomes Reduces Neointimal Formation After Balloon Injury in Rats and Rabbits Circulation, July 30, 2002; 106(5): 599 - 605. [Abstract] [Full Text] [PDF]
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A. Buffon, L. M. Biasucci, G. Liuzzo, G. D'Onofrio, F. Crea, and A. Maseri Widespread Coronary Inflammation in Unstable Angina N. Engl. J. Med., July 4, 2002; 347(1): 5 - 12. [Abstract] [Full Text] [PDF]
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R. P. Choudhury, V. Fuster, J. J. Badimon, E. A. Fisher, and Z. A. Fayad MRI and Characterization of Atherosclerotic Plaque: Emerging Applications and Molecular Imaging Arterioscler Thromb Vasc Biol, July 1, 2002; 22(7): 1065 - 1074. [Abstract] [Full Text] [PDF]
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E. Ivan, J. J. Khatri, C. Johnson, R. Magid, D. Godin, S. Nandi, S. Lessner, and Z. S. Galis Expansive Arterial Remodeling Is Associated With Increased Neointimal Macrophage Foam Cell Content: The Murine Model of Macrophage-Rich Carotid Artery Lesions Circulation, June 4, 2002; 105(22): 2686 - 2691. [Abstract] [Full Text] [PDF]
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 J. A. Ardans, A. P. Economou, J. M. Martinson Jr., M. Zhou, and L. M. Wahl Oxidized low-density and high-density lipoproteins regulate the production of matrix metalloproteinase-1 and -9 by activated monocytes J. Leukoc. Biol., June 1, 2002; 71(6): 1012 - 1018. [Abstract] [Full Text] [PDF]
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U. Kelkenberg, A. H. Wagner, J. Sarhaddar, M. Hecker, and H. E. von der Leyen CCAAT/Enhancer-Binding Protein Decoy Oligodeoxynucleotide Inhibition of Macrophage-Rich Vascular Lesion Formation in Hypercholesterolemic Rabbits Arterioscler Thromb Vasc Biol, June 1, 2002; 22(6): 949 - 954. [Abstract] [Full Text] [PDF]
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F. Nappo, K. Esposito, M. Cioffi, G. Giugliano, A. M. Molinari, G. Paolisso, R. Marfella, and D. Giugliano Postprandial endothelial activation in healthy subjects and in type 2 diabetic patients: Role of fat and carbohydrate meals J. Am. Coll. Cardiol., April 3, 2002; 39(7): 1145 - 1150. [Abstract] [Full Text] [PDF]
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S. Abou-Raya, A. Naeem, H. A.-E. Kheir, and S. El Beltagy Coronary Artery Disease and Periodontal Disease: Is There a Link? Angiology, March 1, 2002; 53(2): 141 - 148. [Abstract] [PDF]
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Z. S. Galis and J. J. Khatri Matrix Metalloproteinases in Vascular Remodeling and Atherogenesis: The Good, the Bad, and the Ugly Circ. Res., February 22, 2002; 90(3): 251 - 262. [Abstract] [Full Text] [PDF]
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A. Braun, B. L. Trigatti, M. J. Post, K. Sato, M. Simons, J. M. Edelberg, R. D. Rosenberg, M. Schrenzel, and M. Krieger Loss of SR-BI Expression Leads to the Early Onset of Occlusive Atherosclerotic Coronary Artery Disease, Spontaneous Myocardial Infarctions, Severe Cardiac Dysfunction, and Premature Death in Apolipoprotein E-Deficient Mice Circ. Res., February 22, 2002; 90(3): 270 - 276. [Abstract] [Full Text] [PDF]
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M. Shimizu, K. Fukuo, S. Nagata, T. Suhara, M. Okuro, K. Fujii, Y. Higashino, M. Mogi, Y. Hatanaka, and T. Ogihara Increased plasma levels of the soluble form of fas ligand in patients with acute myocardial infarction and unstable angina pectoris J. Am. Coll. Cardiol., February 20, 2002; 39(4): 585 - 590. [Abstract] [Full Text] [PDF]
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M. de Lorgeril, P. Salen, P. Defaye, P. Mabo, and F. Paillard Dietary prevention of sudden cardiac death Eur. Heart J., February 2, 2002; 23(4): 277 - 285. [Full Text] [PDF]
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A. H.M Moons, M. Levi, and R. J.G Peters Tissue factor and coronary artery disease Cardiovasc Res, February 1, 2002; 53(2): 313 - 325. [Abstract] [Full Text] [PDF]
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P. N. Seshiah, D. J. Kereiakes, S. S. Vasudevan, N. Lopes, B. Y. Su, N. A. Flavahan, and P. J. Goldschmidt-Clermont Activated Monocytes Induce Smooth Muscle Cell Death: Role of Macrophage Colony-Stimulating Factor and Cell Contact Circulation, January 15, 2002; 105(2): 174 - 180. [Abstract] [Full Text] [PDF]
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M. Takemoto and J. K. Liao Pleiotropic Effects of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors Arterioscler Thromb Vasc Biol, November 1, 2001; 21(11): 1712 - 1719. [Abstract] [Full Text] [PDF]
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M. P. Herman, G. K. Sukhova, P. Libby, N. Gerdes, N. Tang, D. B. Horton, M. Kilbride, R. E. Breitbart, M. Chun, and U. Schonbeck Expression of Neutrophil Collagenase (Matrix Metalloproteinase-8) in Human Atheroma: A Novel Collagenolytic Pathway Suggested by Transcriptional Profiling Circulation, October 16, 2001; 104(16): 1899 - 1904. [Abstract] [Full Text] [PDF]
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X.-Q. Zhao, C. Yuan, T. S. Hatsukami, E. H. Frechette, X.-J. Kang, K. R. Maravilla, and B. G. Brown Effects of Prolonged Intensive Lipid-Lowering Therapy on the Characteristics of Carotid Atherosclerotic Plaques In Vivo by MRI: A Case-Control Study Arterioscler Thromb Vasc Biol, October 1, 2001; 21(10): 1623 - 1629. [Abstract] [Full Text] [PDF]
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F. Tomai, F. Crea, A. Gaspardone, F. Versaci, A. S. Ghini, L. Chiariello, and P. A. Gioffre Unstable Angina and Elevated C-Reactive Protein Levels Predict Enhanced Vasoreactivity of the Culprit Lesion Circulation, September 25, 2001; 104(13): 1471 - 1476. [Abstract] [Full Text] [PDF]
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E.G. Zouridakis, R. Schwartzman, X. Garcia-Moll, I.D. Cox, S. Fredericks, D.W. Holt, and J.C. Kaski Increased plasma endothelin levels in angina patients with rapid coronary artery disease progression Eur. Heart J., September 1, 2001; 22(17): 1578 - 1584. [Abstract] [PDF]
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Z. G. Nadareishvili, D. E. Koziol, B. Szekely, C. Ruetzler, R. LaBiche, R. McCarron, T. J. DeGraba, and S. Jander Increased CD8+ T Cells Associated With Chlamydia pneumoniae in Symptomatic Carotid Plaque Editorial Comment Stroke, September 1, 2001; 32(9): 1966 - 1972. [Abstract] [Full Text] [PDF]
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Z. A. Fayad and V. Fuster Clinical Imaging of the High-Risk or Vulnerable Atherosclerotic Plaque Circ. Res., August 17, 2001; 89(4): 305 - 316. [Abstract] [Full Text] [PDF]
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D. A. Smith, S. D. Irving, J. Sheldon, D. Cole, and J. C. Kaski Serum Levels of the Antiinflammatory Cytokine Interleukin-10 Are Decreased in Patients With Unstable Angina Circulation, August 14, 2001; 104(7): 746 - 749. [Abstract] [Full Text] [PDF]
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J.F. Bentzon and E. Falk Coronary plaques calling for action -- why, where and how many? Eur. Heart J. Suppl., August 1, 2001; 3(suppl_I): I3 - I9. [Abstract] [PDF]
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J.C. Kaski and E.G. Zouridakis Inflammation, infection and acute coronary plaque events Eur. Heart J. Suppl., August 1, 2001; 3(suppl_I): I10 - I15. [Abstract] [PDF]
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L. Badimon, G. Vilahur, S. Sanchez, and X. Duran Atheromatous plaque formation and thrombogenesis: formation, risk factors and therapeutic approaches Eur. Heart J. Suppl., August 1, 2001; 3(suppl_I): I16 - I22. [Abstract] [PDF]
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J. Kusunoki, D. K. Hansoty, K. Aragane, J. T. Fallon, J. J. Badimon, and E. A. Fisher Acyl-CoA:Cholesterol Acyltransferase Inhibition Reduces Atherosclerosis in Apolipoprotein E-Deficient Mice Circulation, May 29, 2001; 103(21): 2604 - 2609. [Abstract] [Full Text] [PDF]
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M. Aikawa and P. Libby Vascular inflammation and activation: new targets for lipid lowering Eur. Heart J. Suppl., May 1, 2001; 3(suppl_B): B3 - B11. [Abstract] [PDF]
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S. Ehara, M. Ueda, T. Naruko, K. Haze, A. Itoh, M. Otsuka, R. Komatsu, T. Matsuo, H. Itabe, T. Takano, et al. Elevated Levels of Oxidized Low Density Lipoprotein Show a Positive Relationship With the Severity of Acute Coronary Syndromes Circulation, April 17, 2001; 103(15): 1955 - 1960. [Abstract] [Full Text] [PDF]
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M. Meuwissen, J. J. Piek, A. C. van der Wal, S. A. J. Chamuleau, K. T. Koch, P. Teeling, C. M. van der Loos, J. G. P. Tijssen, and A. E. Becker Recurrent unstable angina after directional coronary atherectomy is related to the extent of initial coronary plaque inflammation J. Am. Coll. Cardiol., April 1, 2001; 37(5): 1271 - 1276. [Abstract] [Full Text] [PDF]
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C. Stefanadis, K. Toutouzas, E. Tsiamis, C. Stratos, M. Vavuranakis, I. Kallikazaros, D. Panagiotakos, and P. Toutouzas Increased local temperature in human coronary atherosclerotic plaques: an independent predictor of clinical outcome in patients undergoing a percutaneous coronary intervention J. Am. Coll. Cardiol., April 1, 2001; 37(5): 1277 - 1283. [Abstract] [Full Text] [PDF]
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F. De Lorenzo, A. Noorani, and V.V. Kakkar Current trends in the management of thromboembolic events QJM, April 1, 2001; 94(4): 179 - 185. [Full Text] [PDF]
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