| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
American Journal of Pathology, Vol 147, 668-677, Copyright © 1995 by American Society for Investigative Pathology
REGULAR ARTICLES |
MD Rekhter and D Gordon
Department of Pathology, University of Michigan, Ann Arbor 48109-0602, USA.
Cell proliferation, an important mechanism of atherosclerotic plaque growth, occurs among smooth muscle, inflammatory cell, and other cell types. We have identified different topographical patterns of cell proliferation in human carotid plaques, based on cell type. Cell proliferation was determined with an antibody to the proliferating cell nuclear antigen (PCNA), combined with cell type-specific antibodies. Despite low levels of overall proliferative activity, the intima displayed more proliferative activity than the underlying media (1.61 +/- 0.35% in intima versus 0.05 +/- 0.03% in media; P < 0.01). The preponderant proliferative cell type in the intima was the monocyte/macrophage (46.0% of PCNA-positive cells), with a minority being smooth muscle alpha-actin-positive (9.7%), microvascular endothelial (14.3%), and T cells (13.1%). Smooth muscle cells were the dominant proliferating cell type in the media (44.4% of PCNA-positive cells versus 20% endothelial cells, 13.0% monocyte/macrophages, and 14.3% T cells). Within the plaque, foam-cell-rich regions mostly displayed proliferation among macrophages (66.5%), whereas in vascularized fields PCNA positivity was almost equally shared by endothelial cells (23.8%), monocyte/macrophages (26.3%), smooth muscle alpha-actin-positive cells (14.0%), and to a lesser extent, T cells (8.2%). Logistic and linear regression analyses also demonstrated that location in foam-cell-rich regions was a significant predictor of proliferation only among monocyte/macrophages, whereas location in vascularized regions was a good predictor of PCNA positivity among both inflammatory and noninflammatory cells. These different patterns of cell type proliferation suggest possibly different distributions of putative responsible growth regulatory factors in human atherosclerosis.
This article has been cited by other articles:
 |
|
 |
|
  T. T. Keller, J. J. van der Meer, P. Teeling, K. van der Sluijs, M. M. Idu, G. F. Rimmelzwaan, M. Levi, A. C. van der Wal, and O. J. de Boer Selective Expansion of Influenza A Virus-Specific T Cells in Symptomatic Human Carotid Artery Atherosclerotic Plaques Stroke, January 1, 2008; 39(1): 174 - 179. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Roy-Chaudhury, V. P. Sukhatme, and A. K. Cheung Hemodialysis Vascular Access Dysfunction: A Cellular and Molecular Viewpoint J. Am. Soc. Nephrol., April 1, 2006; 17(4): 1112 - 1127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. L. Chan, N. Pejnovic, H. Hamilton, T. V. Liew, D. Popadic, A. Poggi, and S. M. Khan Atherosclerotic Abdominal Aortic Aneurysm and the Interaction Between Autologous Human Plaque-Derived Vascular Smooth Muscle Cells, Type 1 NKT, and Helper T Cells Circ. Res., April 1, 2005; 96(6): 675 - 683. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Rupp, T. Hellwig-Burgel, V. Wobbe, U. Seitzer, E. Brandt, and M. Maass Chlamydia pneumoniae infection promotes a proliferative phenotype in the vasculature through Egr-1 activation in vitro and in vivo PNAS, March 1, 2005; 102(9): 3447 - 3452. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Andres Control of vascular cell proliferation and migration by cyclin-dependent kinase signalling: new perspectives and therapeutic potential Cardiovasc Res, July 1, 2004; 63(1): 11 - 21. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-S. Lee, C.-W. Liu, S.-H. Juan, Y.-C. Liang, P.-Y. Ho, and Y.-H. Lee Molecular Mechanism of Progesterone-Induced Antiproliferation in Rat Aortic Smooth Muscle Cells Endocrinology, July 1, 2003; 144(7): 2785 - 2790. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Hundal, A. Gomez-Munoz, J. Y. Kong, B. S. Salh, A. Marotta, V. Duronio, and U. P. Steinbrecher Oxidized Low Density Lipoprotein Inhibits Macrophage Apoptosis by Blocking Ceramide Generation, Thereby Maintaining Protein Kinase B Activation and Bcl-XL Levels J. Biol. Chem., June 27, 2003; 278(27): 24399 - 24408. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Hamilton Nondisposable materials, chronic inflammation, and adjuvant action J. Leukoc. Biol., June 1, 2003; 73(6): 702 - 712. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Hundal, B. S. Salh, J. W. Schrader, A. Gomez-Munoz, V. Duronio, and U. P. Steinbrecher Oxidized low density lipoprotein inhibits macrophage apoptosis through activation of the PI 3-kinase/PKB pathway J. Lipid Res., September 1, 2001; 42(9): 1483 - 1491. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-Y. Fan, K. S. Ramos, and R. S. Chapkin Dietary {{gamma}}-Linolenic Acid Suppresses Aortic Smooth Muscle Cell Proliferation and Modifies Atherosclerotic Lesions in Apolipoprotein E Knockout Mice J. Nutr., June 1, 2001; 131(6): 1675 - 1681. [Abstract] [Full Text]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 A. P. Burke, F. D. Kolodgie, A. Farb, D. K. Weber, G. T. Malcom, J. Smialek, and R. Virmani Healed Plaque Ruptures and Sudden Coronary Death : Evidence That Subclinical Rupture Has a Role in Plaque Progression Circulation, February 20, 2001; 103(7): 934 - 940. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Aikawa, E. Rabkin, S. Sugiyama, S. J. Voglic, Y. Fukumoto, Y. Furukawa, M. Shiomi, F. J. Schoen, and P. Libby An HMG-CoA Reductase Inhibitor, Cerivastatin, Suppresses Growth of Macrophages Expressing Matrix Metalloproteinases and Tissue Factor In Vivo and In Vitro Circulation, January 16, 2001; 103(2): 276 - 283. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Hamilton, G. Whitty, and W. Jessup Oxidized LDL Can Promote Human Monocyte Survival Arterioscler. Thromb. Vasc. Biol., October 1, 2000; 20 (10): 2329 - 2331. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Melian, Y.-J. Geng, G. K. Sukhova, P. Libby, and S. A. Porcelli CD1 Expression in Human Atherosclerosis : A Potential Mechanism for T Cell Activation by Foam Cells Am. J. Pathol., September 1, 1999; 155(3): 775 - 786. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Martens, M. Lougheed, A. Gomez-Munoz, and U. P. Steinbrecher A Modification of Apolipoprotein B Accounts for Most of the Induction of Macrophage Growth by Oxidized Low Density Lipoprotein J. Biol. Chem., April 16, 1999; 274(16): 10903 - 10910. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
E. Lutgens, M. Daemen, M. Kockx, P. Doevendans, M. Hofker, L. Havekes, H. Wellens, and E. D. de Muinck Atherosclerosis in APOE*3-Leiden Transgenic Mice : From Proliferative to Atheromatous Stage Circulation, January 19, 1999; 99(2): 276 - 283. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Hamilton, D. Myers, W. Jessup, F. Cochrane, R. Byrne, G. Whitty, and S. Moss Oxidized LDL Can Induce Macrophage Survival, DNA Synthesis, and Enhanced Proliferative Response to CSF-1 and GM-CSF Arterioscler. Thromb. Vasc. Biol., January 1, 1999; 19(1): 98 - 105. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D. Rekhter, G. W. Hicks, D. W. Brammer, C. W. Work, J.-S. Kim, D. Gordon, J. A. Keiser, and M. J. Ryan Animal Model That Mimics Atherosclerotic Plaque Rupture Circ. Res., October 5, 1998; 83(7): 705 - 713. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
J. S. Martens, N. E. Reiner, P. Herrera-Velit, and U. P. Steinbrecher Phosphatidylinositol 3-Kinase Is Involved in the Induction of Macrophage Growth by Oxidized Low Density Lipoprotein J. Biol. Chem., February 27, 1998; 273(9): 4915 - 4920. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Brandl, T. Richter, K. Haug, M. G. Wilhelm, P. C. Maurer, and W. Nathrath Topographic Analysis of Proliferative Activity in Carotid Endarterectomy Specimens by Immunocytochemical Detection of the Cell Cycle–Related Antigen Ki-67 Circulation, November 18, 1997; 96(10): 3360 - 3368. [Abstract] [Full Text]
|
|
|
|
|
|
L. Capron, J. Jarnet, D. Heudes, D. Joseph-Monrose, and P. Bruneval Repeated Balloon Injury of Rat Aorta : A Model of Neointima With Attenuated Inhibition by Heparin Arterioscler. Thromb. Vasc. Biol., September 1, 1997; 17(9): 1649 - 1656. [Abstract] [Full Text]
|
|
|
|
|
|
D. Zhang, W. Tang, P. M. Yao, C. Yang, B. Xie, S. Jackowski, and I. Tabas Macrophages Deficient in CTP:Phosphocholine Cytidylyltransferase-alpha Are Viable under Normal Culture Conditions but Are Highly Susceptible to Free Cholesterol-induced Death. MOLECULAR GENETIC EVIDENCE THAT THE INDUCTION OF PHOSPHATIDYLCHOLINE BIOSYNTHESIS IN FREE CHOLESTEROL-LOADED MACROPHAGES IS AN ADAPTIVE RESPONSE J. Biol. Chem., November 3, 2000; 275(45): 35368 - 35376. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
