This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (41) Citing Articles via Google Scholar Google Scholar Articles by Mauriello, A. Articles by Spagnoli, L. G. Search for Related Content PubMed PubMed Citation Articles by Mauriello, A. Articles by Spagnoli, L. G. Related Collections Related Article

CLINICAL RESEARCH: PLAQUE RUPTURE

Diffuse and Active Inflammation Occurs in Both Vulnerable and Stable Plaques of the Entire Coronary Tree

A Histopathologic Study of Patients Dying of Acute Myocardial Infarction

Alessandro Mauriello, MD^_*, Giuseppe Sangiorgi, MD, FESC, Stefano Fratoni, MD^_*, Giampiero Palmieri, MD^_*, Elena Bonanno, MD^_*, Lucia Anemona, MD^_*, Robert S. Schwartz, MD, FACC, FAHA and Luigi Giusto Spagnoli, MD^_*,_*

^_* Department of Pathology, University of Rome Tor Vergata, Rome, Italy
Department of Cardiovascular Diseases, University of Rome Tor Vergata, Rome, Italy
Minnesota Cardiovascular Research Institute, Minneapolis Heart Institute Foundation, Minneapolis, Minnesota

Manuscript received August 12, 2004; revised manuscript received December 20, 2004, accepted January 17, 2005.

^_* Reprint requests and correspondence: Prof. Luigi Giusto Spagnoli, Cattedra di Anatomia ed Istologia Patologica, Dipartimento di Biopatologia e Diagnostica per Immagini, Universita di Roma Tor Vergata, Via Montpellier 1, 00133 Roma, Italy (Email: spagnoli{at}uniroma2.it).

OBJECTIVES: This study was undertaken to define and compare geographic coronary artery inflammation in patients who were dying of acute myocardial infarction (AMI), chronic stable angina (SA), and noncardiac causes (CTRL).

BACKGROUND: Biochemical markers and flow cytometry provide indirect evidence of diffuse coronary inflammation in patients dying of acute coronary syndromes. Yet no histopathologic studies have corroborated these findings. A key unanswered question is whether the inflammatory burden involves the entire coronary tree or is limited to a few plaques.

METHODS: We examined 544 coronary artery segments from 16 patients with AMI, 109 segments from 5 patients with SA, and 304 coronary segments from 9 patients with CTRL.

RESULTS: An average of 6.8 ± 0.5 vulnerable segments per patient were found in the AMI group (in addition to culprit lesions) compared with an average of 0.8 ± 0.3 and 1.4 ± 0.3 vulnerable lesions/patient in the SA and CTRL groups, respectively. The AMI group, independent of the type of plaque observed, showed significantly more inflammatory infiltrates compared with the SA and CTRL groups (121.6 ± 12.4 cell x mm² vs. 37.3 ± 11.9 cell x mm² vs. 26.6 ± 6.8 cell x mm², p = 0.0001). In AMI patients, active inflammation was not only evident within the culprit lesion and vulnerable plaques but also involved stable plaques. These showed a three- to four-fold higher inflammation than vulnerable and stable plaques from the SA and CTRL groups, respectively.

CONCLUSIONS: This histopathologic study found that both vulnerable and stable coronary plaques of patients dying of AMI are diffusely infiltrated by inflammatory cells.

Abbreviations and Acronyms   AMI = acute myocardial infarction   CTRL = controls, death of noncardiac causes   IRA = infarct-related coronary artery   non-IRA = non-infarct-related coronary arteries   SA = chronic stable angina

Related Article

Act Local, Act Global: Inflammation and the Multiplicity of "Vulnerable" Coronary Plaques

Peter Libby
J. Am. Coll. Cardiol. 2005 45: 1600-1602. [Full Text] [PDF]

This article has been cited by other articles:

				I. Laitinen, A. Saraste, E. Weidl, T. Poethko, A. W. Weber, S. G. Nekolla, P. Leppanen, S. Yla-Herttuala, G. Holzlwimmer, A. Walch, et al. Evaluation of {alpha}v{beta}3 Integrin-Targeted Positron Emission Tomography Tracer 18F-Galacto-RGD for Imaging of Vascular Inflammation in Atherosclerotic Mice Circ Cardiovasc Imaging, July 1, 2009; 2(4): 331 - 338. [Abstract] [Full Text] [PDF]

				J. H.F. Rudd, F. Hyafil, and Z. A. Fayad Inflammation Imaging in Atherosclerosis Arterioscler Thromb Vasc Biol, July 1, 2009; 29(7): 1009 - 1016. [Abstract] [Full Text] [PDF]

				F. Hyafil, J.-C. Cornily, J. H.F. Rudd, J. Machac, L. J. Feldman, and Z. A. Fayad Quantification of Inflammation Within Rabbit Atherosclerotic Plaques Using the Macrophage-Specific CT Contrast Agent N1177: A Comparison with 18F-FDG PET/CT and Histology J. Nucl. Med., June 1, 2009; 50(6): 959 - 965. [Abstract] [Full Text] [PDF]

				S. E. Nissen The Vulnerable Plaque "Hypothesis": Promise, but Little Progress J. Am. Coll. Cardiol. Img., April 1, 2009; 2(4): 483 - 485. [Full Text] [PDF]

				A Abbate, R Bussani, G Liuzzo, G G L Biondi-Zoccai, E Barresi, P Mellone, G Sinagra, A Dobrina, F De Giorgio, R Sharma, et al. Sudden coronary death, fatal acute myocardial infarction and widespread coronary and myocardial inflammation Heart, June 1, 2008; 94(6): 737 - 742. [Abstract] [Full Text] [PDF]

				T. J. Bunch, C. S. Rihal, R. J. Gumina, L. Cooper, and N. M. Caplice Progression of Nonculprit Plaque Stenosis Following Successful Percutaneous Intervention Angiology, May 1, 2008; 59(2): 236 - 239. [Abstract] [PDF]

				L. G. Spagnoli, E. Bonanno, G. Sangiorgi, and A. Mauriello Role of Inflammation in Atherosclerosis J. Nucl. Med., November 1, 2007; 48(11): 1800 - 1815. [Abstract] [Full Text] [PDF]

				G. Liuzzo, L. M. Biasucci, G. Trotta, S. Brugaletta, M. Pinnelli, G. Digianuario, V. Rizzello, A. G. Rebuzzi, C. Rumi, A. Maseri, et al. Unusual CD4+CD28null T Lymphocytes and Recurrence of Acute Coronary Events J. Am. Coll. Cardiol., October 9, 2007; 50(15): 1450 - 1458. [Abstract] [Full Text] [PDF]

				O. C. Raffel, G. J. Tearney, D. D. Gauthier, E. F. Halpern, B. E. Bouma, and I.-K. Jang Relationship Between a Systemic Inflammatory Marker, Plaque Inflammation, and Plaque Characteristics Determined by Intravascular Optical Coherence Tomography Arterioscler Thromb Vasc Biol, August 1, 2007; 27(8): 1820 - 1827. [Abstract] [Full Text] [PDF]

				S. B. Yeon, A. Sabir, M. Clouse, P. O. Martinezclark, D. C. Peters, T. H. Hauser, C. M. Gibson, R. Nezafat, D. Maintz, W. J. Manning, et al. Delayed-Enhancement Cardiovascular Magnetic Resonance Coronary Artery Wall Imaging: Comparison With Multislice Computed Tomography and Quantitative Coronary Angiography J. Am. Coll. Cardiol., July 31, 2007; 50(5): 441 - 447. [Abstract] [Full Text] [PDF]

				L. G. Spagnoli, S. Pucci, E. Bonanno, A. Cassone, F. Sesti, A. Ciervo, and A. Mauriello Persistent Chlamydia pneumoniae Infection of Cardiomyocytes Is Correlated with Fatal Myocardial Infarction Am. J. Pathol., January 1, 2007; 170(1): 33 - 42. [Abstract] [Full Text] [PDF]

				C. Napoli, L. O. Lerman, F. de Nigris, M. Gossl, M. L. Balestrieri, and A. Lerman Rethinking Primary Prevention of Atherosclerosis-Related Diseases Circulation, December 5, 2006; 114(23): 2517 - 2527. [Full Text] [PDF]

				J.-F. Surmely, K. Nasu, H. Fujita, M. Terashima, T. Matsubara, E. Tsuchikane, M. Ehara, Y. Kinoshita, Q. X. Zheng, N. Tanaka, et al. Coronary plaque composition of culprit/target lesions according to the clinical presentation: a virtual histology intravascular ultrasound analysis Eur. Heart J., December 2, 2006; 27(24): 2939 - 2944. [Abstract] [Full Text] [PDF]

				N. Eldrup, M.-L. M. Gronholdt, H. Sillesen, and B. G. Nordestgaard Elevated Matrix Metalloproteinase-9 Associated With Stroke or Cardiovascular Death in Patients With Carotid Stenosis Circulation, October 24, 2006; 114(17): 1847 - 1854. [Abstract] [Full Text] [PDF]

				E. Van De Graaff, M. Dutta, P. Das, E. A. Shry, P. D. Frederick, M. Blaney, D. J. Pasta, and S. R. Steinhubl Early Coronary Revascularization Diminishes the Risk of Ischemic Stroke With Acute Myocardial Infarction Stroke, October 1, 2006; 37(10): 2546 - 2551. [Abstract] [Full Text] [PDF]

				S. B. Feinstein Contrast Ultrasound Imaging of the Carotid Artery Vasa Vasorum and Atherosclerotic Plaque Neovascularization J. Am. Coll. Cardiol., July 18, 2006; 48(2): 236 - 243. [Abstract] [Full Text] [PDF]

				M. Exner, E. Minar, W. Mlekusch, S. Sabeti, J. Amighi, W. Lalouschek, G. Maurer, C. Bieglmayer, H. Kieweg, O. Wagner, et al. Myeloperoxidase Predicts Progression of Carotid Stenosis in States of Low High-Density Lipoprotein Cholesterol J. Am. Coll. Cardiol., June 6, 2006; 47(11): 2212 - 2218. [Abstract] [Full Text] [PDF]

				A. N. DeMaria, O. Ben-Yehuda, D. Berman, G. K. Feld, G. S. Ginsburg, B. H. Greenberg, W. Y.W. Lew, D. Sahn, and S. Tsimikas Highlights of the Year in JACC 2005 J. Am. Coll. Cardiol., January 3, 2006; 47(1): 184 - 202. [Full Text] [PDF]

				L. G. Futterman and L. Lemberg Regular Physical Exercise Reduces Cardiovascular Risks Am. J. Crit. Care., January 1, 2006; 15(1): 99 - 102. [Full Text] [PDF]

				M. Schwaiger, S. Ziegler, and S. G. Nekolla PET/CT: Challenge for Nuclear Cardiology J. Nucl. Med., October 1, 2005; 46(10): 1664 - 1678. [Abstract] [Full Text] [PDF]

				P. Libby Act Local, Act Global: Inflammation and the Multiplicity of "Vulnerable" Coronary Plaques J. Am. Coll. Cardiol., May 17, 2005; 45(10): 1600 - 1602. [Full Text] [PDF]