Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:2200-2208
© 1997 American Heart Association, Inc.
Articles |
Fas Is Expressed in Human Atherosclerotic Intima and Promotes Apoptosis of Cytokine-Primed Human Vascular Smooth Muscle Cells
From the Vascular Medicine and Atherosclerosis Unit, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.
Correspondence to Yong-Jian Geng, MD, PhD, Vascular Medicine and Atherosclerosis Unit, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115.
Abstract The membrane protein Fas/Apo-1/CD95 signals
programmed cell death or apoptosis in activated T
lymphocytes. Vascular smooth muscle cells (SMCs) bear markers of
programmed cell death or apoptosis in advanced atherosclerotic
plaques that contain immune cells eg, macrophages and T
lymphocytes. This study tested the hypothesis that the Fas
death-signaling pathway contributes to apoptosis of SMCs
exposed to proinflammatory cytokines produced by these immune
cells during atherogenesis. All atherosclerotic plaques examined (n=14)
contained immunoreactive Fas. The majority of the Fas+ SMCs
localized in the intima of the plaques, whereas the medial SMCs
expressed Fas antigen less prominently. Double staining for DNA
fragments (TUNEL) and Fas or cell identification markers colocalized
Fas with TUNEL+ SMCs in the areas that contained
CD3+ T cells and CD68+ macrophages,
suggesting a role for Fas in the induction of SMC apoptosis by
activated T cells during atherogenesis. In culture, stimulation
with interferon-
, tumor necrosis factor-
, and interleukin-1ß
increased expression of Fas in SMCs. Incubation with an activating
anti-Fas antibody triggered apoptosis of the
cytokine-primed but not the untreated SMCs, as demonstrated by
TUNEL and electrophoresis of oligonucleosomal DNA fragments. These data
suggest that activation of the Fas death-signaling pathway contributes
to the induction of SMC apoptosis during atherogenesis and
furnish a mechanism whereby immune cells and their
cytokines promote this cell death process related to vascular
remodeling and plaque rupture.
Key Words: atherosclerosis • smooth muscle cells • CD95 • T cells • cytokines • apoptosis
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P. Aukrust, F. Muller, T. Ueland, T. Berget, E. Aaser, A. Brunsvig, N. O. Solum, K. Forfang, S. S. Froland, and L. Gullestad Enhanced Levels of Soluble and Membrane-Bound CD40 Ligand in Patients With Unstable Angina : Possible Reflection of T Lymphocyte and Platelet Involvement in the Pathogenesis of Acute Coronary Syndromes Circulation, August 10, 1999; 100(6): 614 - 620. [Abstract] [Full Text] [PDF]
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S. N. Orlov, N. Thorin-Trescases, S. V. Kotelevtsev, J. Tremblay, and P. Hamet Inversion of the Intracellular Na+/K+ Ratio Blocks Apoptosis in Vascular Smooth Muscle at a Site Upstream of Caspase-3 J. Biol. Chem., June 4, 1999; 274(23): 16545 - 16552. [Abstract] [Full Text] [PDF]
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M. R Bennett Apoptosis of vascular smooth muscle cells in vascular remodelling and atherosclerotic plaque rupture Cardiovasc Res, February 1, 1999; 41(2): 361 - 368. [Abstract] [Full Text] [PDF]
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E. Lutgens, E. D. de Muinck, P. J.E.H.M. Kitslaar, J. H.M. Tordoir, H. J.J. Wellens, and M. J.A.P. Daemen Biphasic pattern of cell turnover characterizes the progression from fatty streaks to ruptured human atherosclerotic plaques Cardiovasc Res, February 1, 1999; 41(2): 473 - 479. [Abstract] [Full Text] [PDF]
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E. L. Henderson, Y.-J. Geng, G. K. Sukhova, A. D. Whittemore, J. Knox, and P. Libby Death of Smooth Muscle Cells and Expression of Mediators of Apoptosis by T Lymphocytes in Human Abdominal Aortic Aneurysms Circulation, January 12, 1999; 99(1): 96 - 104. [Abstract] [Full Text] [PDF]
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M. M. Kockx Apoptosis in the Atherosclerotic Plaque : Quantitative and Qualitative Aspects Arterioscler Thromb Vasc Biol, October 1, 1998; 18(10): 1519 - 1522. [Abstract] [Full Text] [PDF]
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M. M. Kockx, G. R. Y. De Meyer, N. Buyssens, M. W. M. Knaapen, H. Bult, and A. G. Herman Cell Composition, Replication, and Apoptosis in Atherosclerotic Plaques After 6 Months of Cholesterol Withdrawal Circ. Res., August 24, 1998; 83(4): 378 - 387. [Abstract] [Full Text] [PDF]
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A. Haunstetter and S. Izumo Apoptosis : Basic Mechanisms and Implications for Cardiovascular Disease Circ. Res., June 15, 1998; 82(11): 1111 - 1129. [Full Text] [PDF]
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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]
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J. H. von der Thusen, B. J.M. van Vlijmen, R. C. Hoeben, M. M. Kockx, L.M. Havekes, T. J.C. van Berkel, and E. A.L. Biessen Induction of Atherosclerotic Plaque Rupture in Apolipoprotein E-/- Mice After Adenovirus-Mediated Transfer of p53 Circulation, April 30, 2002; 105(17): 2064 - 2070. [Abstract] [Full Text] [PDF]
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