© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Apoptosis in atherosclerosis: beneficial or detrimental?
aDepartment of Pathology, A.Z. Middelheim, Lindendreef 1, B-2020 Antwerp, Belgium
bDivision of Pharmacology, University of Antwerp, Antwerp, Belgium
* Corresponding author. Tel.: +32-3-280-4815; fax: +32-3-280-4816 mark.kockx{at}uia.ua.ac.be
Several groups have demonstrated apoptotic cell death in atherosclerotic plaques. The significance of apoptosis in atherosclerosis depends on the stage of the plaque, localization and the cell types involved. Both macrophages and smooth muscle cells undergo apoptosis in atherosclerotic plaques. Apoptosis of macrophages is mainly present in regions showing signs of DNA synthesis/repair. Smooth muscle cell apoptosis is mainly present in less cellular regions and is not associated with DNA synthesis/repair. Even in early stages of atherosclerosis smooth muscle cells become susceptible to undergoing apoptosis since they increase different pro-apoptotic factors. Moreover, recent data indicate that smooth muscle cells may be killed by activated macrophages. The loss of the smooth muscle cells can be detrimental for plaque stability since most of the interstitial collagen fibers, which are important for the tensile strength of the fibrous cap, are produced by SMC. Apoptosis of macrophages could be beneficial for plaque stability if apoptotic bodies are removed. Apoptotic cells that are not scavenged in the plaque activate thrombin which could further induce intraplaque thrombosis. It can be concluded that apoptosis in the primary atherosclerosis is detrimental since it could lead to plaque rupture and thrombosis. Recent data of our group indicate that apoptosis decreases after lipid lowering which could be important in our understanding of the cell biology of plaque stabilization.
KEYWORDS Atherosclerosis; Apoptosis; Smooth muscle; Macrophages; Lipid metabolism
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|
|
|
|
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|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
G. R.Y. De Meyer, D. M.M. De Cleen, S. Cooper, M. W.M. Knaapen, D. M. Jans, W. Martinet, A. G. Herman, H. Bult, and M. M. Kockx Platelet Phagocytosis and Processing of {beta}-Amyloid Precursor Protein as a Mechanism of Macrophage Activation in Atherosclerosis Circ. Res., June 14, 2002; 90(11): 1197 - 1204. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Lambert, N. Malik, L. Shepherd, J. Gunn, S. E. Francis, A. King, D. C. Crossman, D. C. Cumberland, and C. M. Holt Localization of c-Myb and Induction of Apoptosis by Antisense Oligonucleotide c-myb After Angioplasty of Porcine Coronary Arteries Arterioscler Thromb Vasc Biol, November 1, 2001; 21(11): 1727 - 1732. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
A. M. Healy, J. J. Schwartz, X. Zhu, B. E. Herrick, B. Varnum, and H. W. Farber Gas 6 promotes Axl-mediated survival in pulmonary endothelial cells Am J Physiol Lung Cell Mol Physiol, June 1, 2001; 280(6): L1273 - L1281. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Mallat and A. Tedgui Current Perspective on the Role of Apoptosis in Atherothrombotic Disease Circ. Res., May 25, 2001; 88(10): 998 - 1003. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-P. DEIGNER, R. CLAUS, G. A. BONATERRA, C. GEHRKE, N. BIBAK, M. BLAESS, M. CANTZ, J. METZ, and R. KINSCHERF Ceramide induces aSMase expression: implications for oxLDL-induced apoptosis FASEB J, March 1, 2001; 15(3): 807 - 814. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Fisher, B. L. Langille, and D. Srivastava Apoptosis During Cardiovascular Development Circ. Res., November 10, 2000; 87(10): 856 - 864. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. NAPOLI, O. QUEHENBERGER, F. DE NIGRIS, P. ABETE, C. K. GLASS, and W. PALINSKI Mildly oxidized low density lipoprotein activates multiple apoptotic signaling pathways in human coronary cells FASEB J, October 1, 2000; 14(13): 1996 - 2007. [Abstract] [Full Text]
|
|
|
|
|
|
G. H. Gibbons and M. J. Pollman Death Receptors, Intimal Disease, and Gene Therapy : Are Therapies That Modify Cell Fate Moving too Fas? Circ. Res., May 26, 2000; 86(10): 1009 - 1012. [Full Text] [PDF]
|
|
|
|
|
|
M. Borgers, L.-M. Voipio-Pulkki, and S. Izumo Apoptosis Cardiovasc Res, February 1, 2000; 45(3): 525 - 527. [Full Text] [PDF]
|
|
|
|
|
|
M. M. Kavurma, F. S. Santiago, E. Bonfoco, and L. M. Khachigian Sp1 Phosphorylation Regulates Apoptosis via Extracellular FasL-Fas Engagement J. Biol. Chem., February 9, 2001; 276(7): 4964 - 4971. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. I. Miller, M.-K. Chang, C. D. Funk, J. R. Feramisco, and J. L. Witztum 12/15-Lipoxygenase Translocation Enhances Site-specific Actin Polymerization in Macrophages Phagocytosing Apoptotic Cells J. Biol. Chem., May 25, 2001; 276(22): 19431 - 19439. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R Kibbe, J. Li, S. Nie, B. M. Choi, I. Kovesdi, A. Lizonova, T. R Billiar, and E. Tzeng Potentiation of nitric oxide-induced apoptosis in p53-/- vascular smooth muscle cells Am J Physiol Cell Physiol, March 1, 2002; 282(3): C625 - C634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Verheye, G. R.Y. De Meyer, G. Van Langenhove, M. W.M. Knaapen, and M. M. Kockx In Vivo Temperature Heterogeneity of Atherosclerotic Plaques Is Determined by Plaque Composition Circulation, April 2, 2002; 105(13): 1596 - 1601. [Abstract] [Full Text] [PDF]
|
|