© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Leucocyte recruitment in rupture prone regions of lipid-rich plaques: a prominent role for neovascularization?
Department of Cardiovascular Pathology, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, Netherlands
* Corresponding author. Tel.: +31-20-5665646; fax: +31-20-6914738; e-mail: m.i.schenker@amc.uva.nl
Objective: Microvessels in atherosclerotic plaques provide an alternative pathway for the recruitment of leucocytes in the lesions. The present study was designed to investigate the potential role of these microvessels in creating vulnerable sites in atherosclerotic plaques. Methods: Thirty-four atherosclerotic plaques were obtained from 25 patients undergoing carotid endartherectomy (n=16), femoral endartherectomy (n=6) and aortic surgery (n=12). Plaques were histologically classified as either lipid-rich (rupture prone, n=21) or fibrous (stable, n=13). Serial cryostat sections were immunohistochemically investigated using monoclonal antibodies against endothelial cells (ULEX-E and F-VIII), vascular endothelial growth factor (VEGF), endothelial adhesion molecules (ICAM-1, VCAM-1, E-Selectin, CD40) and inflammatory cells (macrophages (CD68) and T lymphocytes (CD3). Results: The microvessel density in lipid-rich plaques was significantly increased as compared to fibrous plaques. Most of these vessels were located in the shoulder-region of the plaque and at the base of the atheroma. Microvessels in lipid-rich plaques also expressed increased levels of ICAM-1, VCAM-1, E-Selectin and CD40. Moreover, inflammation was most abundantly present in the proximity of microvessels. VEGF was only observed on vessels and mononuclear cells in lipid-rich plaques, suggesting that this factor may play a role in microvessels formation. Conclusions: Neovascularisation and expression of adhesion molecules by microvessels at sites of vulnerable lipid-rich plaques may sustain the influx of inflammatory cells and hence, could contribute to plaque destabilization.
KEYWORDS Atherosclerosis; Inflammation; Adhesion molecules; Plaque stability
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. A. Ronald, Y. Chen, A. J.-L. Belisle, A. M. Hamilton, K. A. Rogers, R. A. Hegele, B. Misselwitz, and B. K. Rutt Comparison of Gadofluorine-M and Gd-DTPA for Noninvasive Staging of Atherosclerotic Plaque Stability Using MRI Circ Cardiovasc Imaging, May 1, 2009; 2(3): 226 - 234. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Winter, S. D. Caruthers, H. Zhang, T. A. Williams, S. A. Wickline, and G. M. Lanza Antiangiogenic synergism of integrin-targeted fumagillin nanoparticles and atorvastatin in atherosclerosis. J. Am. Coll. Cardiol. Img., September 1, 2008; 1(5): 624 - 634. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Greve and K. Wachtell Review: Does lowering cholesterol have an impact on the progression of aortic stenosis? Therapeutic Advances in Cardiovascular Disease, August 1, 2008; 2(4): 277 - 286. [Abstract] [PDF]
|
|
|
|
 |
|
 C. Burtea, S. Laurent, O. Murariu, D. Rattat, G. Toubeau, A. Verbruggen, D. Vansthertem, L. Vander Elst, and R. N. Muller Molecular imaging of {alpha}v{beta}3 integrin expression in atherosclerotic plaques with a mimetic of RGD peptide grafted to Gd-DTPA Cardiovasc Res, April 1, 2008; 78(1): 148 - 157. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Leclercq, X. Houard, M. Philippe, V. Ollivier, U. Sebbag, O. Meilhac, and J.-B. Michel Involvement of intraplaque hemorrhage in atherothrombosis evolution via neutrophil protease enrichment J. Leukoc. Biol., December 1, 2007; 82(6): 1420 - 1429. [Abstract] [Full Text] [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]
|
|
|
|
 |
|
 M. Gossl, L. O. Lerman, and A. Lerman Frontiers in Nephrology: Early Atherosclerosis A View Beyond the Lumen J. Am. Soc. Nephrol., November 1, 2007; 18(11): 2836 - 2842. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Doyle and N. Caplice Plaque Neovascularization and Antiangiogenic Therapy for Atherosclerosis J. Am. Coll. Cardiol., May 29, 2007; 49(21): 2073 - 2080. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Petrovan, C. D. Kaplan, R. A. Reisfeld, and L. K. Curtiss DNA Vaccination Against VEGF Receptor 2 Reduces Atherosclerosis in LDL Receptor-Deficient Mice Arterioscler Thromb Vasc Biol, May 1, 2007; 27(5): 1095 - 1100. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. S. Kerwin, K. D. O'Brien, M. S. Ferguson, N. Polissar, T. S. Hatsukami, and C. Yuan Inflammation in Carotid Atherosclerotic Plaque: A Dynamic Contrast-enhanced MR Imaging Study Radiology, November 1, 2006; 241(2): 459 - 468. [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]
|
|
|
|
|
|
P. R. Moreno, K-R. Purushothaman, M. Sirol, A. P. Levy, and V. Fuster Neovascularization in Human Atherosclerosis Circulation, May 9, 2006; 113(18): 2245 - 2252. [Full Text] [PDF]
|
|
|
|
 |
|
 R Krishna Kumar and K R Balakrishnan Influence of lumen shape and vessel geometry on plaque stresses: possible role in the increased vulnerability of a remodelled vessel and the "shoulder" of a plaque Heart, November 1, 2005; 91(11): 1459 - 1465. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Khurana, M. Simons, J. F. Martin, and I. C. Zachary Role of Angiogenesis in Cardiovascular Disease: A Critical Appraisal Circulation, September 20, 2005; 112(12): 1813 - 1824. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Methe, S. Brunner, D. Wiegand, M. Nabauer, J. Koglin, and E. R. Edelman Enhanced T-Helper-1 Lymphocyte Activation Patterns in Acute Coronary Syndromes J. Am. Coll. Cardiol., June 21, 2005; 45(12): 1939 - 1945. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Takaya, C. Yuan, B. Chu, T. Saam, N. L. Polissar, G. P. Jarvik, C. Isaac, J. McDonough, C. Natiello, R. Small, et al. Presence of Intraplaque Hemorrhage Stimulates Progression of Carotid Atherosclerotic Plaques: A High-Resolution Magnetic Resonance Imaging Study Circulation, May 31, 2005; 111(21): 2768 - 2775. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Reinhardt, P. Schaarschmidt, A. Bossert, A. Luske, G. Finkenzeller, T. Mertens, and D. Michel Upregulation of functionally active vascular endothelial growth factor by human cytomegalovirus J. Gen. Virol., January 1, 2005; 86(1): 23 - 30. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. R. Moreno, K. R. Purushothaman, V. Fuster, D. Echeverri, H. Truszczynska, S. K. Sharma, J. J. Badimon, and W. N. O'Connor Plaque Neovascularization Is Increased in Ruptured Atherosclerotic Lesions of Human Aorta: Implications for Plaque Vulnerability Circulation, October 5, 2004; 110(14): 2032 - 2038. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Lappalainen, P. Laine, M. O. Pentikainen, A. Sajantila, and P. T. Kovanen Mast Cells in Neovascularized Human Coronary Plaques Store and Secrete Basic Fibroblast Growth Factor, a Potent Angiogenic Mediator Arterioscler Thromb Vasc Biol, October 1, 2004; 24(10): 1880 - 1885. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Wallner, C. Li, P. K. Shah, K.-J. Wu, S. M. Schwartz, and B. G. Sharifi EGF-Like Domain of Tenascin-C Is Proapoptotic for Cultured Smooth Muscle Cells Arterioscler Thromb Vasc Biol, August 1, 2004; 24(8): 1416 - 1421. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Mazzone, M. C. Epistolato, R. De Caterina, S. Storti, S. Vittorini, S. Sbrana, J. Gianetti, S. Bevilacqua, M. Glauber, A. Biagini, et al. Neoangiogenesis, T-lymphocyte infiltration, and heat shock protein-60 are biological hallmarks of an immunomediated inflammatory process in end-stage calcified aortic valve stenosis J. Am. Coll. Cardiol., May 5, 2004; 43(9): 1670 - 1676. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Chu, A. Kampschulte, M. S. Ferguson, W. S. Kerwin, V. L. Yarnykh, K. D. O'Brien, N. L. Polissar, T. S. Hatsukami, and C. Yuan Hemorrhage in the Atherosclerotic Carotid Plaque: A High-Resolution MRI Study Stroke, May 1, 2004; 35(5): 1079 - 1084. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Martin-Ventura, L. M. Blanco-Colio, B. Munoz-Garcia, A. Gomez-Hernandez, A. Arribas, L. Ortega, J. Tunon, and J. Egido NF-{kappa}B Activation and Fas Ligand Overexpression in Blood and Plaques of Patients With Carotid Atherosclerosis: Potential Implication in Plaque Instability Stroke, February 1, 2004; 35(2): 458 - 463. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. E. Szmitko, C.-H. Wang, R. D. Weisel, J. R. de Almeida, T. J. Anderson, and S. Verma New Markers of Inflammation and Endothelial Cell Activation: Part I Circulation, October 21, 2003; 108(16): 1917 - 1923. [Full Text] [PDF]
|
|
|
|
|
|
O. J de Boer, A. E Becker, and A. C van der Wal T lymphocytes in atherogenesis--functional aspects and antigenic repertoire Cardiovasc Res, October 15, 2003; 60(1): 78 - 86. [Full Text] [PDF]
|
|
|
|
|
|
M. M. Kockx, K. M. Cromheeke, M. W.M. Knaapen, J. M. Bosmans, G. R.Y. De Meyer, A. G. Herman, and H. Bult Phagocytosis and Macrophage Activation Associated With Hemorrhagic Microvessels in Human Atherosclerosis Arterioscler Thromb Vasc Biol, March 1, 2003; 23(3): 440 - 446. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Kerwin, A. Hooker, M. Spilker, P. Vicini, M. Ferguson, T. Hatsukami, and C. Yuan Quantitative Magnetic Resonance Imaging Analysis of Neovasculature Volume in Carotid Atherosclerotic Plaque Circulation, February 18, 2003; 107(6): 851 - 856. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. P. Choudhury, V. Fuster, J. J. Badimon, E. A. Fisher, and Z. A. Fayad MRI and Characterization of Atherosclerotic Plaque: Emerging Applications and Molecular Imaging Arterioscler Thromb Vasc Biol, July 1, 2002; 22(7): 1065 - 1074. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Franz Alber, J. Dulak, M. Frick, W. Dichtl, S. Paul Schwarzacher, O. Pachinger, and F. Weidinger Atorvastatin decreases vascular endothelial growth factor in patients with coronary artery disease J. Am. Coll. Cardiol., June 19, 2002; 39(12): 1951 - 1955. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Nakajima, S. Schulte, K. J. Warrington, S. L. Kopecky, R. L. Frye, J. J. Goronzy, and C. M. Weyand T-Cell-Mediated Lysis of Endothelial Cells in Acute Coronary Syndromes Circulation, February 5, 2002; 105(5): 570 - 575. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Schonbeck and P. Libby CD40 Signaling and Plaque Instability Circ. Res., December 7, 2001; 89(12): 1092 - 1103. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Inoue, H. Itoh, T. Tanaka, T.-H. Chun, K. Doi, Y. Fukunaga, N. Sawada, J. Yamshita, K. Masatsugu, T. Saito, et al. Oxidized LDL Regulates Vascular Endothelial Growth Factor Expression in Human Macrophages and Endothelial Cells Through Activation of Peroxisome Proliferator-Activated Receptor-{{gamma}} Arterioscler Thromb Vasc Biol, April 1, 2001; 21(4): 560 - 566. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. VASILE, Y. TOMITA, L. F. BROWN, O. KOCHER, and H. F. DVORAK Differential expression of thymosin {beta}-10 by early passage and senescent vascular endothelium is modulated by VPF/VEGF: evidence for senescent endothelial cells in vivo at sites of atherosclerosis FASEB J, February 1, 2001; 15(2): 458 - 466. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. J. de Boer, A. C. van der Wal, M. A. Houtkamp, J. M. Ossewaarde, P. Teeling, and A. E. Becker Unstable atherosclerotic plaques contain T-cells that respond to Chlamydia pneumoniae Cardiovasc Res, December 1, 2000; 48(3): 402 - 408. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Sinnaeve, O. Varenne, D. Collen, and S. Janssens Gene therapy in the cardiovascular system: an update Cardiovasc Res, December 1, 1999; 44(3): 498 - 506. [Abstract] [Full Text] [PDF]
|
|