© 1998 American Heart Association, Inc.
Original Contributions |
Complement C6 Deficiency Protects Against Diet-Induced Atherosclerosis in Rabbits
From the Department for Cardiovascular Surgery, University of Mainz (W.S., J.K., H.O.); the Department of Anatomy and Cell Biology III (R.K., H.K., J.M.) and the Institute of Pharmaceutical Chemistry (H.-P.D., O.N.), University of Heidelberg; and the Institute of Medical Microbiology and Hygiene, University of Mainz (S.B.), Germany.
Correspondence to Sucharit Bhakdi, Institute of Medical Microbiology and Hygiene, Hochhaus am Augustusplatz, D-55101 Mainz, Germany. E-mail makowiec{at}mail.uni-mainz.de
Abstract—Low-density lipoprotein (LDL) can be transformed to an atherogenic moiety by nonoxidative, enzymatic degradation. Enzymatically degraded LDL induces macrophage foam cell formation, provokes release of cytokines, and also activates complement. To determine whether complement activation may contribute to atherogenesis, 6 pairs of homozygous C6-deficient rabbits and their non–C6-deficient heterozygous siblings were fed a cholesterol-rich diet for 14 weeks. Cholesterol levels and plasma lipoprotein profiles of the animals in the C6-competent and C6-deficient groups did not significantly differ, and the high density lipoprotein and LDL cholesterol ratios at the end of the experiment were 0.07±0.01 and 0.08±0.01 (SEM), respectively. However, differences in atherosclerotic plaque formation were discernible macroscopically, with extensive aortic lesions being visible in all C6-competent animals and absent in all C6-deficient animals. Aortas were sectioned from thorax to abdomen, and 10 sections were stained from each aorta. Quantification of atherosclerotic lesions and lumen stenosis with the use of computer-based morphometry documented a dramatic protective effect of C6 deficiency on the development of diet-induced atherosclerosis. We conclude that the terminal complement sequence is centrally involved in atherosclerotic lesion progression.
Key Words: complement activation • atherosclerosis
This article has been cited by other articles:
 |
|
 |
|
  V. W.Y. Leung, S. Yun, M. Botto, J. C. Mason, T. H. Malik, W. Song, D. Paixao-Cavalcante, M. C. Pickering, J. J. Boyle, and D. O. Haskard Decay-Accelerating Factor Suppresses Complement C3 Activation and Retards Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice Am. J. Pathol., October 1, 2009; 175(4): 1757 - 1767. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Matthijsen, M. P.J. de Winther, D. Kuipers, I. van der Made, C. Weber, M. V. Herias, M. J.J. Gijbels, and W. A. Buurman Macrophage-Specific Expression of Mannose-Binding Lectin Controls Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice Circulation, April 28, 2009; 119(16): 2188 - 2195. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Wu, W. Hu, A. Shahsafaei, W. Song, M. Dobarro, G. K. Sukhova, R. R. Bronson, G.-p. Shi, R. P. Rother, J. A. Halperin, et al. Complement Regulator CD59 Protects Against Atherosclerosis by Restricting the Formation of Complement Membrane Attack Complex Circ. Res., February 27, 2009; 104(4): 550 - 558. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Shagdarsuren, K. Bidzhekov, Y. Djalali-Talab, E. A. Liehn, M. Hristov, R. A. Matthijsen, W. A. Buurman, A. Zernecke, and C. Weber C1-Esterase Inhibitor Protects Against Neointima Formation After Arterial Injury in Atherosclerosis-Prone Mice Circulation, January 1, 2008; 117(1): 70 - 78. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Verdeguer, C. Castro, M. Kubicek, D. Pla, M. Vila-Caballer, A. Vinue, F. Civeira, M. Pocovi, J. J. Calvete, and V. Andres Complement regulation in murine and human hypercholesterolemia and role in the control of macrophage and smooth muscle cell proliferation Cardiovasc Res, November 1, 2007; 76(2): 340 - 350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. K. Bhatia, S. Yun, V. Leung, D. C. Grimsditch, G. M. Benson, M. B. Botto, J. J. Boyle, and D. O. Haskard Complement C1q Reduces Early Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice Am. J. Pathol., January 1, 2007; 170(1): 416 - 426. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. K. Hansson Epidemiology Complements Immunology in the Heart Arterioscler Thromb Vasc Biol, October 1, 2006; 26(10): 2178 - 2180. [Full Text] [PDF]
|
|
|
|
|
|
S.-R. Ji, Y. Wu, L. A. Potempa, Y.-H. Liang, and J. Zhao Effect of Modified C-Reactive Protein on Complement Activation: A Possible Complement Regulatory Role of Modified or Monomeric C-Reactive Protein in Atherosclerotic Lesions Arterioscler Thromb Vasc Biol, April 1, 2006; 26(4): 935 - 941. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M Carter Inflammation, thrombosis and acute coronary syndromes Diabetes and Vascular Disease Research, October 1, 2005; 2(3): 113 - 121. [Abstract] [PDF]
|
|
|
|
|
|
K. Reifenberg, H.-A. Lehr, D. Baskal, E. Wiese, S. C. Schaefer, S. Black, D. Samols, M. Torzewski, K. J. Lackner, M. Husmann, et al. Role of C-Reactive Protein in Atherogenesis: Can the Apolipoprotein E Knockout Mouse Provide the Answer? Arterioscler Thromb Vasc Biol, August 1, 2005; 25(8): 1641 - 1646. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Persson, J. Boren, A.-K. L. Robertson, V. Wallenius, G. K. Hansson, and M. Pekna Lack of Complement Factor C3, but Not Factor B, Increases Hyperlipidemia and Atherosclerosis in Apolipoprotein E-/- Low-Density Lipoprotein Receptor-/- Mice Arterioscler Thromb Vasc Biol, June 1, 2004; 24(6): 1062 - 1067. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bhakdi, M. Torzewski, K. Paprotka, S. Schmitt, H. Barsoom, P. Suriyaphol, S.-R. Han, K. J. Lackner, and M. Husmann Possible Protective Role for C-Reactive Protein in Atherogenesis: Complement Activation by Modified Lipoproteins Halts Before Detrimental Terminal Sequence Circulation, April 20, 2004; 109(15): 1870 - 1876. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.M. Hirschfield and M.B. Pepys C-reactive protein and cardiovascular disease: new insights from an old molecule QJM, November 1, 2003; 96(11): 793 - 807. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Oksjoki, H. Jarva, P. T. Kovanen, P. Laine, S. Meri, and M. O. Pentikainen Association Between Complement Factor H and Proteoglycans in Early Human Coronary Atherosclerotic Lesions: Implications for Local Regulation of Complement Activation Arterioscler Thromb Vasc Biol, April 1, 2003; 23(4): 630 - 636. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Buono, C. E. Come, J. L. Witztum, G. F. Maguire, P. W. Connelly, M. Carroll, and A. H. Lichtman Influence of C3 Deficiency on Atherosclerosis Circulation, June 25, 2002; 105(25): 3025 - 3031. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-A. Lehr, T. A. Sagban, C. Ihling, U. Zahringer, K.-D. Hungerer, M. Blumrich, K. Reifenberg, and S. Bhakdi Immunopathogenesis of Atherosclerosis: Endotoxin Accelerates Atherosclerosis in Rabbits on Hypercholesterolemic Diet Circulation, August 21, 2001; 104(8): 914 - 920. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Urbich, M. Fritzenwanger, A. M. Zeiher, and S. Dimmeler Laminar Shear Stress Upregulates the Complement-Inhibitory Protein Clusterin : A Novel Potent Defense Mechanism Against Complement-Induced Endothelial Cell Activation Circulation, February 1, 2000; 101(4): 352 - 355. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D. Collard, A. Agah, W. Reenstra, J. Buras, and G. L. Stahl Endothelial Nuclear Factor-{kappa}B Translocation and Vascular Cell Adhesion Molecule-1 Induction by Complement : Inhibition With Anti-Human C5 Therapy or cGMP Analogues Arterioscler Thromb Vasc Biol, November 1, 1999; 19(11): 2623 - 2629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bhakdi, M. Torzewski, M. Klouche, and M. Hemmes Complement and Atherogenesis : Binding of CRP to Degraded, Nonoxidized LDL Enhances Complement Activation Arterioscler Thromb Vasc Biol, October 1, 1999; 19(10): 2348 - 2354. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Klouche, A. E. May, M. Hemmes, M. Meßner, S. M. Kanse, K. T. Preissner, and S. Bhakdi Enzymatically Modified, Nonoxidized LDL Induces Selective Adhesion and Transmigration of Monocytes and T-Lymphocytes Through Human Endothelial Cell Monolayers Arterioscler Thromb Vasc Biol, March 1, 1999; 19(3): 784 - 793. [Abstract] [Full Text] [PDF]
|
|