| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 1996;94:2787-2792.)
© 1996 American Heart Association, Inc.
Articles |
the Wihuri Research Institute (M.K., P.T.K.) and the Department of Forensic Medicine, University of Helsinki (A.P.), Helsinki, Finland.
Correspondence to Petri T. Kovanen, MD, Wihuri Research Institute, Kalliolinnantie 4, 00140 Helsinki, Finland.
Background Mast cells, a cell type involved in inflammatory reactions, are present in coronary atheromas and localize to the erosion or rupture site of atheromas in myocardial infarction. Here we report the presence of TNF-
, a proinflammatory cytokine, in mast cells of human coronary atheromas.
Methods and Results From samples of 37 coronary arteries from subjects autopsied for medicolegal reasons, sections of the bifurcation area of the left coronary artery were stained immunohistochemically for mast cells and TNF-
. In addition, macrophages, T lymphocytes, smooth muscle cells, and endothelial cells were investigated for their content of TNF-
. In normal intimas and fatty streaks, none of the cell types studied were TNF-
positive. In 14 of the 24 atheromas found, TNF-
positive cells were present. Of the total number of mast cells, 23% stained for TNF-
; of the macrophages, 1.3%; and of the smooth muscle cells, 0.4%. The majority (55%) of TNF-
positive mast cells in the atheromas were located in the shoulder region and the remaining 35% in the cap and 10% in the core regions. Immunoelectron microscopy showed that the TNF-
in mast cells resided within their cytoplasmic secretory granules, demonstrating that these cells contain stores of TNF-
that will be released on degranulation.
Conclusions This study demonstrates the presence of mast cells with TNF-
containing secretory granules, particularly in the shoulder region of human coronary atheromas. By releasing their TNF-
, mast cells may play an active role in the inflammatory reactions of these rupture-prone areas of atheromas.
Key Words: atherosclerosis coronary disease cells cytokines
This article has been cited by other articles:
![]() |
X. Tan, S. Essengue, J. Talreja, J. Reese, D. J. Stechschulte, and K. N. Dileepan Histamine Directly and Synergistically with Lipopolysaccharide Stimulates Cyclooxygenase-2 Expression and Prostaglandin I2 and E2 Production in Human Coronary Artery Endothelial Cells J. Immunol., December 1, 2007; 179(11): 7899 - 7906. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Bot, S. C.A. de Jager, A. Zernecke, K. A. Lindstedt, T. J.C. van Berkel, C. Weber, and E. A.L. Biessen Perivascular Mast Cells Promote Atherogenesis and Induce Plaque Destabilization in Apolipoprotein E-Deficient Mice Circulation, May 15, 2007; 115(19): 2516 - 2525. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. B. Olszewski, A. J. Groot, J. Dastych, and E. F. Knol TNF Trafficking to Human Mast Cell Granules: Mature Chain-Dependent Endocytosis J. Immunol., May 1, 2007; 178(9): 5701 - 5709. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Zernichow, M. Abrink, J. Hallgren, M. Grujic, G. Pejler, and S. O. Kolset Serglycin Is the Major Secreted Proteoglycan in Macrophages and Has a Role in the Regulation of Macrophage Tumor Necrosis Factor-{alpha} Secretion in Response to Lipopolysaccharide J. Biol. Chem., September 15, 2006; 281(37): 26792 - 26801. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. A. VanderLaan and C. A. Reardon Thematic review series: The Immune System and Atherogenesis. The unusual suspects:an overview of the minor leukocyte populations in atherosclerosis J. Lipid Res., May 1, 2005; 46(5): 829 - 838. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. A. Lindstedt, M. J. Leskinen, and P. T. Kovanen Proteolysis of the Pericellular Matrix: A Novel Element Determining Cell Survival and Death in the Pathogenesis of Plaque Erosion and Rupture Arterioscler Thromb Vasc Biol, August 1, 2004; 24(8): 1350 - 1358. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. A Doggrell and J. C Wanstall Vascular chymase: pathophysiological role and therapeutic potential of inhibition Cardiovasc Res, March 1, 2004; 61(4): 653 - 662. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Kishore, C. Luedemann, E. Bord, D. Goukassian, and D. W. Losordo Tumor Necrosis Factor-Mediated E2F1 Suppression in Endothelial Cells: Differential Requirement of c-Jun N-Terminal Kinase and p38 Mitogen-Activated Protein Kinase Signal Transduction Pathways Circ. Res., November 14, 2003; 93(10): 932 - 940. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. M. Fernandez-Real and W. Ricart Insulin Resistance and Chronic Cardiovascular Inflammatory Syndrome Endocr. Rev., June 1, 2003; 24(3): 278 - 301. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. H. Von der Thusen, J. Kuiper, T. J. C. Van Berkel, and E. A. L. Biessen Interleukins in Atherosclerosis: Molecular Pathways and Therapeutic Potential Pharmacol. Rev., March 1, 2003; 55(1): 133 - 166. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. S. Forrester Prevention of Plaque Rupture: A New Paradigm of Therapy Ann Intern Med, November 19, 2002; 137(10): 823 - 833. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Kishore, I. Spyridopoulos, C. Luedemann, and D. W. Losordo Functionally Novel Tumor Necrosis Factor-{alpha}-Modulated CHR-Binding Protein Mediates Cyclin A Transcriptional Repression in Vascular Endothelial Cells Circ. Res., August 23, 2002; 91(4): 307 - 314. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. L. Brower, A. L. Chancey, S. Thanigaraj, B. B. Matsubara, and J. S. Janicki Cause and effect relationship between myocardial mast cell number and matrix metalloproteinase activity Am J Physiol Heart Circ Physiol, August 1, 2002; 283(2): H518 - H525. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. H Chester Mast cells feel the strain Cardiovasc Res, July 1, 2002; 55(1): 13 - 15. [Full Text] [PDF] |
||||
![]() |
S. A. Schreyer, C. M. Vick, and R. C. LeBoeuf Loss of Lymphotoxin-alpha but Not Tumor Necrosis Factor-alpha Reduces Atherosclerosis in Mice J. Biol. Chem., March 29, 2002; 277(14): 12364 - 12368. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. L. King, S. J. Szilvassy, and A. Daugherty Interleukin-4 Deficiency Decreases Atherosclerotic Lesion Formation in a Site-Specific Manner in Female LDL Receptor-/- Mice Arterioscler Thromb Vasc Biol, March 1, 2002; 22(3): 456 - 461. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. P. Metsarinne, P. Vehmaan-Kreula, P. T. Kovanen, O. Saijonmaa, M. Baumann, Y. Wang, T. Nyman, F. Y. Fyhrquist, and K. K. Eklund Activated Mast Cells Increase the Level of Endothelin-1 mRNA in Cocultured Endothelial Cells and Degrade the Secreted Peptide Arterioscler Thromb Vasc Biol, February 1, 2002; 22(2): 268 - 273. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. S. Elkind, J. Cheng, B. Boden-Albala, T. Rundek, J. Thomas, H. Chen, L. E. Rabbani, R. L. Sacco, and A. G. Thrift Tumor Necrosis Factor Receptor Levels Are Associated With Carotid Atherosclerosis * Editorial Comment Stroke, January 1, 2002; 33(1): 31 - 38. [Abstract] [Full Text] [PDF] |
||||
![]() |
W.-H. Lee, S.-H. Kim, Y. Lee, B. B. Lee, B. Kwon, H. Song, B. S. Kwon, and J.-E. Park Tumor Necrosis Factor Receptor Superfamily 14 Is Involved in Atherogenesis by Inducing Proinflammatory Cytokines and Matrix Metalloproteinases Arterioscler Thromb Vasc Biol, December 1, 2001; 21(12): 2004 - 2010. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Leskinen, Y. Wang, D. Leszczynski, K. A. Lindstedt, and P. T. Kovanen Mast Cell Chymase Induces Apoptosis of Vascular Smooth Muscle Cells Arterioscler Thromb Vasc Biol, April 1, 2001; 21(4): 516 - 522. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Tintut, J. Patel, F. Parhami, and L. L. Demer Tumor Necrosis Factor-{alpha} Promotes In Vitro Calcification of Vascular Cells via the cAMP Pathway Circulation, November 21, 2000; 102(21): 2636 - 2642. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Genovese, J.-P. Bouvet, G. Florio, B. Lamparter-Schummert, L. Bjorck, and G. Marone Bacterial Immunoglobulin Superantigen Proteins A and L Activate Human Heart Mast Cells by Interacting with Immunoglobulin E Infect. Immun., October 1, 2000; 68(10): 5517 - 5524. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Schieffer, E. Schieffer, D. Hilfiker-Kleiner, A. Hilfiker, P. T. Kovanen, M. Kaartinen, J. Nussberger, W. Harringer, and H. Drexler Expression of Angiotensin II and Interleukin 6 in Human Coronary Atherosclerotic Plaques : Potential Implications for Inflammation and Plaque Instability Circulation, March 28, 2000; 101(12): 1372 - 1378. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Krishnaswamy, D. S. Chi, and J. Kelley Vulnerable Plaque Ann Intern Med, September 7, 1999; 131(5): 392 - 393. [Full Text] [PDF] |
||||
![]() |
A. de Paulis, G. Minopoli, E. Arbustini, G. de Crescenzo, F. Dal Piaz, P. Pucci, T. Russo, and G. Marone Stem Cell Factor Is Localized in, Released from, and Cleaved by Human Mast Cells J. Immunol., September 1, 1999; 163(5): 2799 - 2808. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. C Newby and A. B Zaltsman Fibrous cap formation or destruction -- the critical importance of vascular smooth muscle cell proliferation, migration and matrix formation Cardiovasc Res, February 1, 1999; 41(2): 345 - 360. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. Spyridopoulos, N. Principe, K. L. Krasinski, S.-h. Xu, M. Kearney, M. Magner, J. M. Isner, and D. W. Losordo Restoration of E2F Expression Rescues Vascular Endothelial Cells From Tumor Necrosis Factor-{alpha}–Induced Apoptosis Circulation, December 22, 1998; 98(25): 2883 - 2890. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. L. Johnson, C. L. Jackson, G. D. Angelini, and S. J. George Activation of Matrix-Degrading Metalloproteinases by Mast Cell Proteases in Atherosclerotic Plaques Arterioscler Thromb Vasc Biol, November 1, 1998; 18(11): 1707 - 1715. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Kaartinen, A. C. van der Wal, C. M. van der Loos, J. J. Piek, K. T. Koch, A. E. Becker, and P. T. Kovanen Mast cell infiltration in acute coronary syndromes: implications for plaque rupture J. Am. Coll. Cardiol., September 1, 1998; 32(3): 606 - 612. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Libby The interface of atherosclerosis and thrombosis: basic mechanisms Vascular Medicine, August 1, 1998; 3(3): 225 - 229. [Abstract] [PDF] |
||||
![]() |
S. Jander, M. Sitzer, R. Schumann, M. Schroeter, M. Siebler, H. Steinmetz, and G. Stoll Inflammation in High-Grade Carotid Stenosis : A Possible Role for Macrophages and T Cells in Plaque Destabilization Stroke, August 1, 1998; 29(8): 1625 - 1630. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. T. Kovanen, M. Manttari, T. Palosuo, V. Manninen, and K. Aho Prediction of Myocardial Infarction in Dyslipidemic Men by Elevated Levels of Immunoglobulin Classes A, E, and G, but Not M Arch Intern Med, July 13, 1998; 158(13): 1434 - 1439. [Abstract] [Full Text] |
||||
|
Circulation Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search Copyright © 1996 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited. |