Arteriosclerosis and Thrombosis, Vol 14, 141-147, Copyright © 1994 by American Heart Association

ARTICLES

Atherosclerosis in mice lacking apo E. Evaluation of lesional development and progression [published erratum appears in Arterioscler Thromb 1994 May;14(5):839]

RL Reddick, SH Zhang and N Maeda
Department of Pathology, School of Medicine, University of North Carolina at Chapel Hill 27599-7525.

Apolipoprotein E-deficient mice have spontaneous elevations of total plasma cholesterol and triglycerides and reduced high-density lipoprotein. The mice develop arterial lesions in a time-dependent manner. Lesional distribution was centered in the aortic sinus in young mice, and the lesions were widely distributed throughout the arterial tree in mice at 8 to 9 months of age. In young mice, subendothelial foam cell deposits were present in the aortic sinus adjacent to valve- attachment sites. By 5 months of age, foam cell deposits, free cholesterol, and admixed smooth muscle cells composed the developing atherosclerotic lesions. After 8 to 9 months of age, the arterial lesions showed increased complexity, and fibrous cap lesions were present. Transmission electron microscopy showed foam cells, smooth muscle cells (both contractile and synthetic varieties), cellular debris, and acicular cholesterol deposits within the plaques. By scanning electron microscopy, subendothelial collections of foam cells were present within the aortic sinus and ascending aorta. The results show that the complexity of the atherosclerotic lesions that develop in these apo E deficient-mice are similar to those described in other species and therefore represent an important model for studies of genetic and environmental influences on the atherosclerotic process.

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				C. A. Reardon, L. Blachowicz, T. White, V. Cabana, Y. Wang, J. Lukens, J. Bluestone, and G. S. Getz Effect of Immune Deficiency on Lipoproteins and Atherosclerosis in Male Apolipoprotein E-Deficient Mice Arterioscler Thromb Vasc Biol, June 1, 2001; 21(6): 1011 - 1016. [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]

				N. Ishimori, K. Iwabuchi, S. Fujii, K. Watano, C. Iwabuchi, M. Ato, H. Chiba, S. Tanaka, A. Kitabatake, and K. Onoé Mixed allogeneic chimerism with wild-type strains ameliorates atherosclerosis in apolipoprotein E-deficient mice J. Leukoc. Biol., May 1, 2001; 69(5): 732 - 740. [Abstract] [Full Text]

				W. Ni, K. Egashira, S. Kitamoto, C. Kataoka, M. Koyanagi, S. Inoue, K. Imaizumi, C. Akiyama, K.-i. Nishida, and A. Takeshita New Anti-Monocyte Chemoattractant Protein-1 Gene Therapy Attenuates Atherosclerosis in Apolipoprotein E-Knockout Mice Circulation, April 24, 2001; 103(16): 2096 - 2101. [Abstract] [Full Text] [PDF]

				T. Claudel, M. D. Leibowitz, C. Fiévet, A. Tailleux, B. Wagner, J. J. Repa, G. Torpier, J.-M. Lobaccaro, J. R. Paterniti, D. J. Mangelsdorf, et al. Reduction of atherosclerosis in apolipoprotein E knockout mice by activation of the retinoid X receptor PNAS, February 15, 2001; (2001) 41609298. [Abstract] [Full Text]

				M. E. Rosenfeld, P. Polinsky, R. Virmani, K. Kauser, G. Rubanyi, and S. M. Schwartz Advanced Atherosclerotic Lesions in the Innominate Artery of the ApoE Knockout Mouse Arterioscler Thromb Vasc Biol, December 1, 2000; 20(12): 2587 - 2592. [Abstract] [Full Text] [PDF]

				M.-C. Bourdillon, R. N. Poston, C. Covacho, E. Chignier, G. Bricca, and J. L. McGregor ICAM-1 Deficiency Reduces Atherosclerotic Lesions in Double-Knockout Mice (ApoE-/-/ICAM-1-/-) Fed a Fat or a Chow Diet Arterioscler Thromb Vasc Biol, December 1, 2000; 20(12): 2630 - 2635. [Abstract] [Full Text] [PDF]

				C. J. Hartley, A. K. Reddy, S. Madala, B. Martin-McNulty, R. Vergona, M. E. Sullivan, M. Halks-Miller, G. E. Taffet, L. H. Michael, M. L. Entman, et al. Hemodynamic changes in apolipoprotein E-knockout mice Am J Physiol Heart Circ Physiol, November 1, 2000; 279(5): H2326 - H2334. [Abstract] [Full Text] [PDF]

				A. Daugherty, S. C. Whitman, A. E. Block, and D. L. Rateri Polymorphism of class A scavenger receptors in C57BL/6 mice J. Lipid Res., October 1, 2000; 41(10): 1568 - 1577. [Abstract] [Full Text]

				W. Shi, X. Wang, N. J. Wang, W. H. McBride, and A. J. Lusis Effect of Macrophage-Derived Apolipoprotein E on Established Atherosclerosis in Apolipoprotein E-Deficient Mice Arterioscler Thromb Vasc Biol, October 1, 2000; 20(10): 2261 - 2266. [Abstract] [Full Text] [PDF]

				K. Zibara, E. Chignier, C. Covacho, R. Poston, G. Canard, P. Hardy, and J. McGregor Modulation of Expression of Endothelial Intercellular Adhesion Molecule-1, Platelet-Endothelial Cell Adhesion Molecule-1, and Vascular Cell Adhesion Molecule-1 in Aortic Arch Lesions of Apolipoprotein E-Deficient Compared With Wild-Type Mice Arterioscler Thromb Vasc Biol, October 1, 2000; 20(10): 2288 - 2296. [Abstract] [Full Text] [PDF]

				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]

				T. Schinke and G. Karsenty Vascular calcification--a passive process in need of inhibitors Nephrol. Dial. Transplant., September 1, 2000; 15(9): 1272 - 1274. [Full Text] [PDF]

				P. Liuba, P. Karnani, E. Pesonen, I. Paakkari, A. Forslid, L. Johansson, K. Persson, T. Wadstrom, and R. Laurini Endothelial Dysfunction After Repeated Chlamydia pneumoniae Infection in Apolipoprotein E-Knockout Mice Circulation, August 29, 2000; 102(9): 1039 - 1044. [Abstract] [Full Text] [PDF]

				F. E. Thorngate, L. L. Rudel, R. L. Walzem, and D. L. Williams Low Levels of Extrahepatic Nonmacrophage ApoE Inhibit Atherosclerosis Without Correcting Hypercholesterolemia in ApoE-Deficient Mice Arterioscler Thromb Vasc Biol, August 1, 2000; 20(8): 1939 - 1945. [Abstract] [Full Text] [PDF]

				C. Desurmont, J.-M. Caillaud, F. Emmanuel, P. Benoit, J. C. Fruchart, G. Castro, D. Branellec, J.-M. Heard, and N. Duverger Complete Atherosclerosis Regression After Human ApoE Gene Transfer in ApoE-Deficient/Nude Mice Arterioscler Thromb Vasc Biol, February 1, 2000; 20(2): 435 - 442. [Abstract] [Full Text] [PDF]

				R. G. Collins, R. Velji, N. V. Guevara, M. J. Hicks, L. Chan, and A. L. Beaudet P-Selectin or Intercellular Adhesion Molecule (Icam)-1 Deficiency Substantially Protects against Atherosclerosis in Apolipoprotein E-Deficient Mice J. Exp. Med., January 3, 2000; 191(1): 189 - 194. [Abstract] [Full Text] [PDF]

				T. Hayek, J. Attias, R. Coleman, S. Brodsky, J. Smith, J. L. Breslow, and S. Keidar The angiotensin-converting enzyme inhibitor, fosinopril, and the angiotensin II receptor antagonist, losartan, inhibit LDL oxidation and attenuate atherosclerosis independent of lowering blood pressure in apolipoprotein E deficient mice Cardiovasc Res, December 1, 1999; 44(3): 579 - 587. [Abstract] [Full Text] [PDF]

				S. Marathe, G. Kuriakose, K. J. Williams, and I. Tabas Sphingomyelinase, an Enzyme Implicated in Atherogenesis, Is Present in Atherosclerotic Lesions and Binds to Specific Components of the Subendothelial Extracellular Matrix Arterioscler Thromb Vasc Biol, November 1, 1999; 19(11): 2648 - 2658. [Abstract] [Full Text] [PDF]

				R. Yang, L. Powell-Braxton, A. K. Ogaoawara, N. Dybdal, S. Bunting, O. Ohneda, and H. Jin Hypertension and Endothelial Dysfunction in Apolipoprotein E Knockout Mice Arterioscler Thromb Vasc Biol, November 1, 1999; 19(11): 2762 - 2768. [Abstract] [Full Text] [PDF]

				T. Arai, F. Rinninger, L. Varban, V. Fairchild-Huntress, C.-P. Liang, W. Chen, T. Seo, R. Deckelbaum, D. Huszar, and A. R. Tall Decreased selective uptake of high density lipoprotein cholesteryl esters in apolipoprotein E knock-out mice PNAS, October 12, 1999; 96(21): 12050 - 12055. [Abstract] [Full Text] [PDF]

				L. Calleja, M. A. Paris, A. Paul, E. Vilella, J. Joven, A. Jimenez, G. Beltran, M. Uceda, N. Maeda, and J. Osada Low-Cholesterol and High-Fat Diets Reduce Atherosclerotic Lesion Development in ApoE-Knockout Mice Arterioscler Thromb Vasc Biol, October 1, 1999; 19(10): 2368 - 2375. [Abstract] [Full Text] [PDF]