Arteriosclerosis and Thrombosis, Vol 14, 133-140, Copyright © 1994 by American Heart Association

ARTICLES

ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree

Y Nakashima, AS Plump, EW Raines, JL Breslow and R Ross
Department of Pathology, University of Washington, Seattle 98195.

Initial description of apolipoprotein (apo) E-deficient transgenic mice demonstrated the development of severe hypercholesterolemia due to probable delayed clearance of large atherogenic particles from the circulation. Examination of these mice demonstrated foam cell accumulation in the aortic root and pulmonary arteries by 10 weeks of age. In the present study, the animals were fed either chow or a high- fat, Western-type diet and examined at ages ranging from 6 to 40 weeks. Gross examination by dissection microscopy revealed a predilection for development of lesions in the aortic root, at the lesser curvature of the aortic arch, the principal branches of the aorta, and in the pulmonary and carotid arteries. Monocyte attachment to endothelial cells was observed by light and electron microscopic examination at 6 weeks, the earliest time point examined. Foam cell lesions developed as early as 8 weeks, and after 15 weeks advanced lesions (fibrous plaques) were observed. The latter consisted of a fibrous cap containing smooth muscle cells surrounded by connective tissue matrix that covered a necrotic core with numerous foamy macrophages. Mice fed the Western- type diet generally had more advanced lesions than those fed a chow diet. The apoE-deficient mouse contains the entire spectrum of lesions observed during atherogenesis and is the first mouse model to develop lesions similar to those in humans. This model should provide numerous opportunities to study the pathogenesis and therapy of atherosclerosis in a small, genetically defined animal.

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				N. R. Veillard, S. Steffens, F. Burger, G. Pelli, and F. Mach Differential Expression Patterns of Proinflammatory and Antiinflammatory Mediators During Atherogenesis in Mice Arterioscler Thromb Vasc Biol, December 1, 2004; 24(12): 2339 - 2344. [Abstract] [Full Text] [PDF]

				M. A. McAteer, J. E. Schneider, K. Clarke, S. Neubauer, K. M. Channon, and R. P. Choudhury Quantification and 3D Reconstruction of Atherosclerotic Plaque Components in Apolipoprotein E Knockout Mice Using Ex Vivo High-Resolution MRI Arterioscler Thromb Vasc Biol, December 1, 2004; 24(12): 2384 - 2390. [Abstract] [Full Text] [PDF]

				A. S. Major, M. T. Wilson, J. L. McCaleb, Y. Ru Su, A. K. Stanic, S. Joyce, L. Van Kaer, S. Fazio, and M. F. Linton Quantitative and Qualitative Differences in Proatherogenic NKT Cells in Apolipoprotein E-Deficient Mice Arterioscler Thromb Vasc Biol, December 1, 2004; 24(12): 2351 - 2357. [Abstract] [Full Text] [PDF]

				B.R. Wamhoff, M.H. Hoofnagle, A. Burns, S. Sinha, O.G. McDonald, and G.K. Owens A G/C Element Mediates Repression of the SM22{alpha} Promoter Within Phenotypically Modulated Smooth Muscle Cells in Experimental Atherosclerosis Circ. Res., November 12, 2004; 95(10): 981 - 988. [Abstract] [Full Text] [PDF]

				W. Shi, H. Pei, J. J. Fischer, J. C. James, J. F. Angle, A. H. Matsumoto, G. A. Helm, and I. J. Sarembock Neointimal formation in two apolipoprotein E-deficient mouse strains with different atherosclerosis susceptibility J. Lipid Res., November 1, 2004; 45(11): 2008 - 2014. [Abstract] [Full Text] [PDF]

				S. M. Lessner, D. E. Martinson, and Z. S. Galis Compensatory Vascular Remodeling During Atherosclerotic Lesion Growth Depends on Matrix Metalloproteinase-9 Activity Arterioscler Thromb Vasc Biol, November 1, 2004; 24(11): 2123 - 2129. [Abstract] [Full Text] [PDF]

				L. Branen, L. Hovgaard, M. Nitulescu, E. Bengtsson, J. Nilsson, and S. Jovinge Inhibition of Tumor Necrosis Factor-{alpha} Reduces Atherosclerosis in Apolipoprotein E Knockout Mice Arterioscler Thromb Vasc Biol, November 1, 2004; 24(11): 2137 - 2142. [Abstract] [Full Text] [PDF]

				A. Recinos III, B. K. Carr, D. B. Bartos, I. Boldogh, J. R. Carmical, L. M. Belalcazar, and A. R. Brasier Liver gene expression associated with diet and lesion development in atherosclerosis-prone mice: induction of components of alternative complement pathway Physiol Genomics, September 16, 2004; 19(1): 131 - 142. [Abstract] [Full Text] [PDF]

				K. S. Moulton, B. R. Olsen, S. Sonn, N. Fukai, D. Zurakowski, and X. Zeng Loss of Collagen XVIII Enhances Neovascularization and Vascular Permeability in Atherosclerosis Circulation, September 7, 2004; 110(10): 1330 - 1336. [Abstract] [Full Text] [PDF]

				E. Trogan, Z. A. Fayad, V. V. Itskovich, J.-G. S. Aguinaldo, V. Mani, J. T. Fallon, I. Chereshnev, and E. A. Fisher Serial Studies of Mouse Atherosclerosis by In Vivo Magnetic Resonance Imaging Detect Lesion Regression After Correction of Dyslipidemia Arterioscler Thromb Vasc Biol, September 1, 2004; 24(9): 1714 - 1719. [Abstract] [Full Text] [PDF]

				Y. Naka, L. G. Bucciarelli, T. Wendt, L. K. Lee, L. L. Rong, R. Ramasamy, S. F. Yan, and A. M. Schmidt RAGE Axis: Animal Models and Novel Insights Into the Vascular Complications of Diabetes Arterioscler Thromb Vasc Biol, August 1, 2004; 24(8): 1342 - 1349. [Abstract] [Full Text] [PDF]

				H. Wientgen, F. E. Thorngate, S. Omerhodzic, L. Rolnitzky, J. T. Fallon, D. L. Williams, and E. A. Fisher Subphysiologic Apolipoprotein E (ApoE) Plasma Levels Inhibit Neointimal Formation After Arterial Injury in ApoE-Deficient Mice Arterioscler Thromb Vasc Biol, August 1, 2004; 24(8): 1460 - 1465. [Abstract] [Full Text] [PDF]

				G. K. Owens, M. S. Kumar, and B. R. Wamhoff Molecular Regulation of Vascular Smooth Muscle Cell Differentiation in Development and Disease Physiol Rev, July 1, 2004; 84(3): 767 - 801. [Abstract] [Full Text] [PDF]

				F. C. Gibson III, C. Hong, H.-H. Chou, H. Yumoto, J. Chen, E. Lien, J. Wong, and C. Attardo Genco Innate Immune Recognition of Invasive Bacteria Accelerates Atherosclerosis in Apolipoprotein E-Deficient Mice Circulation, June 8, 2004; 109(22): 2801 - 2806. [Abstract] [Full Text] [PDF]

				M. D. Brown, L. Jin, M.-L. Jien, A. H. Matsumoto, G. A. Helm, A. J. Lusis, J. S. Frank, and W. Shi Lipid retention in the arterial wall of two mouse strains with different atherosclerosis susceptibility J. Lipid Res., June 1, 2004; 45(6): 1155 - 1161. [Abstract] [Full Text] [PDF]

				K. S. Meir and E. Leitersdorf Atherosclerosis in the Apolipoprotein E-Deficient Mouse: A Decade of Progress Arterioscler Thromb Vasc Biol, June 1, 2004; 24(6): 1006 - 1014. [Abstract] [Full Text] [PDF]

				S. Upadhya, S. Mooteri, N. Peckham, and R. G. Pai Atherogenic Effect of Interleukin-2 and Antiatherogenic Effect of Interleukin-2 Antibody in Apo-E-Deficient Mice Angiology, May 1, 2004; 55(3): 289 - 294. [Abstract] [PDF]

				W. Ni, S. Kitamoto, M. Ishibashi, M. Usui, S. Inoue, K.-i. Hiasa, Q. Zhao, K.-i. Nishida, A. Takeshita, and K. Egashira Monocyte Chemoattractant Protein-1 Is an Essential Inflammatory Mediator in Angiotensin II-Induced Progression of Established Atherosclerosis in Hypercholesterolemic Mice Arterioscler Thromb Vasc Biol, March 1, 2004; 24(3): 534 - 539. [Abstract] [Full Text]

				E. Harja, L. G. Bucciarelli, Y. Lu, D. M. Stern, Y. S. Zou, A. M. Schmidt, and S.-F. Yan Early Growth Response-1 Promotes Atherogenesis: Mice Deficient in Early Growth Response-1 and Apolipoprotein E Display Decreased Atherosclerosis and Vascular Inflammation Circ. Res., February 20, 2004; 94(3): 333 - 339. [Abstract] [Full Text] [PDF]

				R. Stocker and R. A O'Halloran Dealcoholized red wine decreases atherosclerosis in apolipoprotein E gene-deficient mice independently of inhibition of lipid peroxidation in the artery wall Am. J. Clinical Nutrition, January 1, 2004; 79(1): 123 - 130. [Abstract] [Full Text] [PDF]

				P. G. Frank, H. Lee, D. S. Park, N. N. Tandon, P. E. Scherer, and M. P. Lisanti Genetic Ablation of Caveolin-1 Confers Protection Against Atherosclerosis Arterioscler Thromb Vasc Biol, January 1, 2004; 24(1): 98 - 105. [Abstract] [Full Text] [PDF]