Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:2106-2112
© 2000 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Vaccine-Induced Antibodies Inhibit CETP Activity In Vivo and Reduce Aortic Lesions in a Rabbit Model of Atherosclerosis
From AVANT Immunotherapeutics, Inc, Needham, Mass, and Boston University Medical Center (A.D.C.), Boston, Mass.
Correspondence to Charles W. Rittershaus, AVANT Immunotherapeutics, Inc, 119 Fourth Ave, Needham, MA 02494. E-mail crittershaus{at}avantimmune.com
Abstract—Using a vaccine approach, we immunized New Zealand White rabbits with a peptide containing a region of cholesteryl ester transfer protein (CETP) known to be required for neutral lipid transfer function. These rabbits had significantly reduced plasma CETP activity and an altered lipoprotein profile. In a cholesterol-fed rabbit model of atherosclerosis, the fraction of plasma cholesterol in HDL was 42% higher and the fraction of plasma cholesterol in LDL was 24% lower in the CETP-vaccinated group than in the control-vaccinated group. Moreover, the percentage of the aorta surface exhibiting atherosclerotic lesion was 39.6% smaller in the CETP-vaccinated rabbits than in controls. The data reported here demonstrate that CETP activity can be reduced in vivo by vaccination with a peptide derived from CETP and support the concept that inhibition of CETP activity in vivo can be antiatherogenic. In addition, these studies suggest that vaccination against a self-antigen is a viable therapeutic strategy for disease management.
Key Words: CETP • lipoproteins • atherosclerosis • vaccine
This article has been cited by other articles:
 |
|
 |
|
  M. Guerin, W. Le Goff, E. Duchene, Z. Julia, T. Nguyen, T. Thuren, C. L. Shear, and M. J. Chapman Inhibition of CETP by Torcetrapib Attenuates the Atherogenicity of Postprandial TG-Rich Lipoproteins in Type IIB Hyperlipidemia Arterioscler. Thromb. Vasc. Biol., January 1, 2008; 28(1): 148 - 154. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. Van Lenten, A. C. Wagner, M. Navab, G. M. Anantharamaiah, S. Hama, S. T. Reddy, and A. M. Fogelman Lipoprotein inflammatory properties and serum amyloid A levels but not cholesterol levels predict lesion area in cholesterol-fed rabbits J. Lipid Res., November 1, 2007; 48(11): 2344 - 2353. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. Hauer, G. H.M. van Puijvelde, N. Peterse, P. de Vos, V. van Weel, E. J.A. van Wanrooij, E. A.L. Biessen, P. H.A. Quax, A. G. Niethammer, R. A. Reisfeld, et al. Vaccination Against VEGFR2 Attenuates Initiation and Progression of Atherosclerosis Arterioscler. Thromb. Vasc. Biol., September 1, 2007; 27(9): 2050 - 2057. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Morehouse, E. D. Sugarman, P.-A. Bourassa, T. M. Sand, F. Zimetti, F. Gao, G. H. Rothblat, and A. J. Milici Inhibition of CETP activity by torcetrapib reduces susceptibility to diet-induced atherosclerosis in New Zealand White rabbits J. Lipid Res., June 1, 2007; 48(6): 1263 - 1272. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Harder, P. Lau, A. Meng, S. C. Whitman, and R. McPherson Cholesteryl Ester Transfer Protein (CETP) Expression Protects Against Diet Induced Atherosclerosis in SR-BI Deficient Mice Arterioscler. Thromb. Vasc. Biol., April 1, 2007; 27(4): 858 - 864. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. K. Shah Inhibition of CETP as a novel therapeutic strategy for reducing the risk of atherosclerotic disease Eur. Heart J., January 1, 2007; 28(1): 5 - 12. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. H. Davidson, J. M. McKenney, C. L. Shear, and J. H. Revkin Efficacy and Safety of Torcetrapib, a Novel Cholesteryl Ester Transfer Protein Inhibitor, in Individuals With Below-Average High-Density Lipoprotein Cholesterol Levels J. Am. Coll. Cardiol., November 7, 2006; 48(9): 1774 - 1781. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. M. Stylianou, S.-W. Tsaih, K. DiPetrillo, N. Ishimori, R. Li, B. Paigen, and G. Churchill Complex Genetic Architecture Revealed by Analysis of High-Density Lipoprotein Cholesterol in Chromosome Substitution Strains and F2 Crosses Genetics, October 1, 2006; 174(2): 999 - 1007. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Kee, D. Caiazza, K.-A. Rye, P.H.R. Barrett, L.A. Morehouse, and P.J. Barter Effect of Inhibiting Cholesteryl Ester Transfer Protein on the Kinetics of High-Density Lipoprotein Cholesteryl Ester Transport in Plasma: In Vivo Studies in Rabbits Arterioscler. Thromb. Vasc. Biol., April 1, 2006; 26(4): 884 - 890. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H.E.M. Klerkx, K. E. Harchaoui, W. A. van der Steeg, S. M. Boekholdt, E. S.G. Stroes, J. J.P. Kastelein, and J. A. Kuivenhoven Cholesteryl Ester Transfer Protein (CETP) Inhibition Beyond Raising High-Density Lipoprotein Cholesterol Levels: Pathways by Which Modulation of CETP Activity May Alter Atherogenesis Arterioscler. Thromb. Vasc. Biol., April 1, 2006; 26(4): 706 - 715. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. W. Clark, R. B. Ruggeri, D. Cunningham, and M. J. Bamberger Description of the torcetrapib series of cholesteryl ester transfer protein inhibitors, including mechanism of action J. Lipid Res., March 1, 2006; 47(3): 537 - 552. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Barter and J. J.P. Kastelein Targeting Cholesteryl Ester Transfer Protein for the Prevention and Management of Cardiovascular Disease J. Am. Coll. Cardiol., February 7, 2006; 47(3): 492 - 499. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Masson, J.-P. Pais de Barros, Z. Zak, T. Gautier, N. Le Guern, M. Assem, J. W. Chisholm, J. R. Paterniti Jr., and L. Lagrost Human apoA-I expression in CETP transgenic rats leads to lower levels of apoC-I in HDL and to magnification of CETP-mediated lipoprotein changes J. Lipid Res., February 1, 2006; 47(2): 356 - 365. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Dumont, T. Gautier, J.-P. P. de Barros, H. Laplanche, D. Blache, P. Ducoroy, J. Fruchart, J.-C. Fruchart, P. Gambert, D. Masson, et al. Molecular Mechanism of the Blockade of Plasma Cholesteryl Ester Transfer Protein by Its Physiological Inhibitor Apolipoprotein CI J. Biol. Chem., November 11, 2005; 280(45): 38108 - 38116. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Shinohara, S. Kawashima, T. Yamashita, T. Takaya, R. Toh, T. Ishida, T. Ueyama, N. Inoue, K.-i. Hirata, and M. Yokoyama Xenogenic smooth muscle cell immunization reduces neointimal formation in balloon-injured rabbit carotid arteries Cardiovasc Res, November 1, 2005; 68(2): 249 - 258. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E Toubi and Y Shoenfeld Predictive and protective autoimmunity in cardiovascular diseases: is vaccination therapy a reality? Lupus, September 1, 2005; 14(9): 665 - 669. [Abstract] [PDF]
|
|
|
|
 |
|
 J. S. Forrester, R. Makkar, and P.K. Shah Increasing High-Density Lipoprotein Cholesterol in Dyslipidemia by Cholesteryl Ester Transfer Protein Inhibition: An Update for Clinicians Circulation, April 12, 2005; 111(14): 1847 - 1854. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Nilsson, G. K. Hansson, and P. K. Shah Immunomodulation of Atherosclerosis: Implications for Vaccine Development Arterioscler. Thromb. Vasc. Biol., January 1, 2005; 25(1): 18 - 28. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. de Grooth, A. H. E. M. Klerkx, E. S. G. Stroes, A. F. H. Stalenhoef, J. J. P. Kastelein, and J. A. Kuivenhoven A review of CETP and its relation to atherosclerosis J. Lipid Res., November 1, 2004; 45(11): 1967 - 1974. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Brousseau, E. J. Schaefer, M. L. Wolfe, L. T. Bloedon, A. G. Digenio, R. W. Clark, J. P. Mancuso, and D. J. Rader Effects of an Inhibitor of Cholesteryl Ester Transfer Protein on HDL Cholesterol N. Engl. J. Med., April 8, 2004; 350(15): 1505 - 1515. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Gotto Jr and E. A. Brinton Assessing low levels of high-density lipoprotein cholesterol as a risk factor in coronary heart disease: A working group report and update J. Am. Coll. Cardiol., March 3, 2004; 43(5): 717 - 724. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. W. Clark, T. A. Sutfin, R. B. Ruggeri, A. T. Willauer, E. D. Sugarman, G. Magnus-Aryitey, P. G. Cosgrove, T. M. Sand, R. T. Wester, J. A. Williams, et al. Raising High-Density Lipoprotein in Humans Through Inhibition of Cholesteryl Ester Transfer Protein: An Initial Multidose Study of Torcetrapib Arterioscler. Thromb. Vasc. Biol., March 1, 2004; 24(3): 490 - 497. [Abstract] [Full Text]
|
|
|
|
|
|
V. M. Paromov and R. E. Morton Lipid Transfer Inhibitor Protein Defines the Participation of High Density Lipoprotein Subfractions in Lipid Transfer Reactions Mediated by Cholesterol Ester Transfer Protein (CETP) J. Biol. Chem., October 17, 2003; 278(42): 40859 - 40866. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Barter, H. B. Brewer Jr, M. J. Chapman, C. H. Hennekens, D. J. Rader, and A. R. Tall Cholesteryl Ester Transfer Protein: A Novel Target for Raising HDL and Inhibiting Atherosclerosis Arterioscler. Thromb. Vasc. Biol., February 1, 2003; 23(2): 160 - 167. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Cazita, J. A. Berti, C. Aoki, M. Gidlund, L. M. Harada, V. S. Nunes, E. C. R. Quintao, and H. C. F. Oliveira Cholesteryl ester transfer protein expression attenuates atherosclerosis in ovariectomized mice J. Lipid Res., January 1, 2003; 44(1): 33 - 40. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Zak, L. Lagrost, T. Gautier, D. Masson, V. Deckert, L. Duverneuil, J.-P. P. de Barros, N. Le Guern, L. Dumont, M. Schneider, et al. Expression of simian CETP in normolipidemic Fisher rats has a profound effect on large sized apoE-containing HDL J. Lipid Res., December 1, 2002; 43(12): 2164 - 2171. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Forrester Prevention of Plaque Rupture: A New Paradigm of Therapy Ann Intern Med, November 19, 2002; 137(10): 823 - 833. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Gautier, D. Masson, M. C. Jong, L. Duverneuil, N. Le Guern, V. Deckert, J.-P. P. de Barros, L. Dumont, A. Bataille, Z. Zak, et al. Apolipoprotein CI Deficiency Markedly Augments Plasma Lipoprotein Changes Mediated by Human Cholesteryl Ester Transfer Protein (CETP) in CETP Transgenic/ApoCI-knocked Out Mice J. Biol. Chem., August 23, 2002; 277(35): 31354 - 31363. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.N. Durrington, B. Mackness, and M.I. Mackness The Hunt for Nutritional and Pharmacological Modulators of Paraoxonase Arterioscler. Thromb. Vasc. Biol., August 1, 2002; 22(8): 1248 - 1250. [Full Text] [PDF]
|
|
|
|
|
|
R. Gander, P. Eller, S. Kaser, I. Theurl, D. Walter, T. Sauper, A. Ritsch, J. R. Patsch, and B. Foger Molecular characterization of rabbit phospholipid transfer protein: choroid plexus and ependyma synthesize high levels of phospholipid transfer protein J. Lipid Res., April 1, 2002; 43(4): 636 - 645. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. K. Shah, S. Kaul, J. Nilsson, and B. Cercek Exploiting the Vascular Protective Effects of High-Density Lipoprotein and its Apolipoproteins: An Idea Whose Time for Testing Is Coming, Part II Circulation, November 13, 2001; 104(20): 2498 - 2502. [Full Text] [PDF]
|
|
|
|
|
|
A. von Eckardstein, J.-R. Nofer, and G. Assmann High Density Lipoproteins and Arteriosclerosis : Role of Cholesterol Efflux and Reverse Cholesterol Transport Arterioscler. Thromb. Vasc. Biol., January 1, 2001; 21(1): 13 - 27. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Barter CETP and Atherosclerosis Arterioscler. Thromb. Vasc. Biol., September 1, 2000; 20(9): 2029 - 2031. [Full Text] [PDF]
|
|
|
|
|
|
G. J. de Grooth, J. A. Kuivenhoven, A. F.H. Stalenhoef, J. de Graaf, A. H. Zwinderman, J. L. Posma, A. van Tol, and J. J.P. Kastelein Efficacy and Safety of a Novel Cholesteryl Ester Transfer Protein Inhibitor, JTT-705, in Humans: A Randomized Phase II Dose-Response Study Circulation, May 7, 2002; 105(18): 2159 - 2165. [Abstract] [Full Text] [PDF]
|
|