© 1995 American Heart Association, Inc.
Articles |
Effect of the Antioxidant N,N'-Diphenyl 1,4-Phenylenediamine (DPPD) on Atherosclerosis in ApoE-Deficient Mice
From the Department of Medicine, University of California San Diego, La Jolla, Calif.
Correspondence to Wulf Palinski, MD, Department of Medicine, 0682, University of California, San Diego, 9500 Gilman Dr, La Jolla, CA 92093-0682.
Abstract Apolipoprotein (apo) E–deficient mice develop atherosclerotic lesions that contain epitopes formed during the oxidative modification of lipoproteins, and they demonstrate high titers of circulating autoantibodies against such epitopes, suggesting that this murine strain may provide a model to investigate the atherogenic mechanisms of oxidized lipoproteins (Palinski et al, Arterioscler Thromb. 1994;14:605-616). To test the hypothesis that lipoprotein oxidation contributes to lesion formation in apoE-deficient mice, we studied the effect of the antioxidant N,N'-diphenyl 1,4-phenylenediamine (DPPD) in mice fed a high-fat diet containing 0.15% cholesterol. Animals were divided into two subgroups matched for sex and plasma cholesterol levels, and DPPD (0.5% wt/wt) was added to the diet of one subgroup. Throughout the 6 months of intervention, DPPD treatment had no significant effect on plasma cholesterol. Plasma levels of DPPD at the end of the experiment were 33.1 µmol/L. As judged by resistance to loss of polyunsaturated fatty acids, lipoproteins (d <1.019 g/mL) from DPPD-treated animals showed greater resistance to copper-induced oxidation than lipoproteins from control animals. In addition, there was a greater than twofold prolongation of the lag time in the formation of conjugated dienes in the LDL and IDL fractions of DPPD-treated mice. Atherosclerosis was significantly reduced, by 36% in the DPPD-treated mice (14.0±4.53% of aortic surface area versus 21.9±11.6%; n=32; P<.02). These results are consistent with the hypothesis that lipoprotein oxidation contributes to atherogenesis in apoE-deficient mice. However, further studies with other antioxidants are needed to validate this hypothesis.
Key Words: lipoproteins, oxidized • antioxidants • mice, gene-targeted • apolipoprotein E • arteriosclerosis
This article has been cited by other articles:
 |
|
 |
|
  L.G Lyngdorf, S Gregersen, A Daugherty, and E Falk Paradoxical reduction of atherosclerosis in apoE-deficient mice with obesity-related type 2 diabetes Cardiovasc Res, October 1, 2003; 59(4): 854 - 862. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Cyrus, L. X. Tang, J. Rokach, G. A. FitzGerald, and D. Pratico Lipid Peroxidation and Platelet Activation in Murine Atherosclerosis Circulation, October 16, 2001; 104(16): 1940 - 1945. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Bentzon, E. Skovenborg, C. Hansen, J. Moller, N. S.-C. de Gaulejac, J. Proch, and E. Falk Red Wine Does Not Reduce Mature Atherosclerosis in Apolipoprotein E-Deficient Mice Circulation, March 27, 2001; 103(12): 1681 - 1687. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Miura, T. Chiba, I. Tomita, H. Koizumi, S. Miura, K. Umegaki, Y. Hara, and M. Ikeda Tea Catechins Prevent the Development of Atherosclerosis in Apoprotein E-Deficient Mice J. Nutr., January 1, 2001; 131(1): 27 - 32. [Abstract] [Full Text]
|
|
|
|
|
|
T. M. Black, P. Wang, N. Maeda, and R. A. Coleman Palm Tocotrienols Protect ApoE +/- Mice from Diet-Induced Atheroma Formation J. Nutr., October 1, 2000; 130(10): 2420 - 2426. [Abstract] [Full Text]
|
|
|
|
|
|
O. A. Levander The Selenium-Coxsackievirus Connection: Chronicle of a Collaboration J. Nutr., February 1, 2000; 130(2): 485 - 485. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. Parthasarathy, N. Santanam, S. Ramachandran, and O. Meilhac Oxidants and antioxidants in atherogenesis: an appraisal J. Lipid Res., December 1, 1999; 40(12): 2143 - 2157. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Fruebis, M. Silvestre, D. Shelton, C. Napoli, and W. Palinski Inhibition of VCAM-1 expression in the arterial wall is shared by structurally different antioxidants that reduce early atherosclerosis in NZW rabbits J. Lipid Res., November 1, 1999; 40(11): 1958 - 1966. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. F. KEANEY JR., D. I. SIMON, and J. E. FREEDMAN Vitamin E and vascular homeostasis: implications for atherosclerosis FASEB J, June 1, 1999; 13(9): 965 - 975. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. Shaish, J. George, B. Gilburd, P. Keren, H. Levkovitz, and D. Harats Dietary ß-Carotene and {alpha}-Tocopherol Combination Does Not Inhibit Atherogenesis in an ApoE–Deficient Mouse Model Arterioscler Thromb Vasc Biol, June 1, 1999; 19(6): 1470 - 1475. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. Moghadasian, B. M. McManus, D. V. Godin, B. Rodrigues, and J. J. Frohlich Proatherogenic and Antiatherogenic Effects of Probucol and Phytosterols in Apolipoprotein E–Deficient Mice : Possible Mechanisms of Action Circulation, April 6, 1999; 99(13): 1733 - 1739. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Crawford, E. A. Kirk, M. E. Rosenfeld, R. C. LeBoeuf, and A. Chait Dietary Antioxidants Inhibit Development of Fatty Streak Lesions in the LDL Receptor–Deficient Mouse Arterioscler Thromb Vasc Biol, September 1, 1998; 18(9): 1506 - 1513. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Bird, R. K. Tangirala, J. Fruebis, D. Steinberg, J. L. Witztum, and W. Palinski Effect of probucol on LDL oxidation and atherosclerosis in LDL receptor-deficient mice J. Lipid Res., May 1, 1998; 39(5): 1079 - 1090. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-J. Wu, C.-Y. Hong, S.-J. Lin, P. Wu, and M.-S. Shiao Increase of Vitamin E Content in LDL and Reduction of Atherosclerosis in Cholesterol-Fed Rabbits by a Water-Soluble Antioxidant-Rich Fraction of Salvia miltiorrhiza Arterioscler Thromb Vasc Biol, March 1, 1998; 18(3): 481 - 486. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Neuzil, J. K. Christison, E. Iheanacho, J.-C. Fragonas, V. Zammit, N. H. Hunt, and R. Stocker Radical-induced lipoprotein and plasma lipid oxidation in normal and apolipoprotein E gene knockout (apoE-/-) mice: apoE-/- mouse as a model for testing the role of tocopherol-mediated peroxidation in atherogenesis J. Lipid Res., February 1, 1998; 39(2): 354 - 368. [Abstract] [Full Text]
|
|
|
|
|
|
J. S. Munday, K. G. Thompson, K. A. C. James, and B. W. Manktelow Dietary Antioxidants Do Not Reduce Fatty Streak Formation in the C57BL/6 Mouse Atherosclerosis Model Arterioscler Thromb Vasc Biol, January 1, 1998; 18(1): 114 - 119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Maor, T. Hayek, R. Coleman, and M. Aviram Plasma LDL Oxidation Leads to Its Aggregation in the Atherosclerotic Apolipoprotein E-Deficient Mice Arterioscler Thromb Vasc Biol, November 1, 1997; 17(11): 2995 - 3005. [Abstract] [Full Text]
|
|
|
|
|
|
J. Fruebis, V. Gonzalez, M. Silvestre, and W. Palinski Effect of Probucol Treatment on Gene Expression of VCAM-1, MCP-1, and M-CSF in the Aortic Wall of LDL Receptor–Deficient Rabbits During Early Atherogenesis Arterioscler Thromb Vasc Biol, July 1, 1997; 17(7): 1289 - 1302. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. Lougheed, C. M. Lum, W. Ling, H. Suzuki, T. Kodama, and U. Steinbrecher High Affinity Saturable Uptake of Oxidized Low Density Lipoprotein by Macrophages from Mice Lacking the Scavenger Receptor Class A Type I/II J. Biol. Chem., May 16, 1997; 272(20): 12938 - 12944. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. L. Hendriks, F. van der Sman-de Beer, B. J.M. van Vlijmen, L. C. van Vark, M. H. Hofker, and L. M. Havekes Uptake by J774 Macrophages of Very-Low-Density Lipoproteins Isolated From ApoE-Deficient Mice Is Mediated by a Distinct Receptor and Stimulated by Lipoprotein Lipase Arterioscler Thromb Vasc Biol, March 1, 1997; 17(3): 498 - 504. [Abstract] [Full Text]
|
|
|
|
|
|
D. Steinberg Lewis A. Conner Memorial Lecture: Oxidative Modification of LDL and Atherogenesis Circulation, February 18, 1997; 95(4): 1062 - 1071. [Full Text]
|
|
|
|
|
|
M. H. Moghadasian, B. M. McManus, P. H. Pritchard, and J. J. Frohlich "Tall Oil"–Derived Phytosterols Reduce Atherosclerosis in ApoE-Deficient Mice Arterioscler Thromb Vasc Biol, January 1, 1997; 17(1): 119 - 126. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Nakata and N. Maeda Vulnerable Atherosclerotic Plaque Morphology in Apolipoprotein E-Deficient Mice Unable to Make Ascorbic Acid Circulation, March 26, 2002; 105(12): 1485 - 1490. [Abstract] [Full Text] [PDF]
|
|