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American Journal of Pathology, Vol 103, 181-190, Copyright © 1981 by American Society for Investigative Pathology
REGULAR ARTICLES |
RG Gerrity
In a previous publication the author and his co-workers demonstrated that atherosclerotic lesion development in the aorta of hypercholesterolemic pigs was preceded by intimal penetration of blood- borne mononuclear cells, and that medial smooth muscle cells were not involved in the formation of early fatty lesions in this model. The current study shows that aortic arch lesions do not progress beyond the fatty cell lesion stage for up to 30 weeks of a moderate cholesterol/lard diet, although they become more extensive in area. Mononuclear cells were found adherent to the endothelium, in endothelial junctions, and in the intima during this period, and were ultrastructurally identified as monocytes by the presence of peroxidase- positive granules (peroxisomes) in their cytoplasm. In addition, lesion areas with nonspecific esterase activity correlated well with Sudan IV staining. Intimal monocytes and altered intimal monocytes with an enlarged cytoplasm and containing a few lipid droplets were both shown to be phagocytic by their uptake of ferritin, which had penetrated the intima after intravenous injection. Circulating monocytes and those adherent to the endothelial surface did not contain ferritin in these animals. The results indicate that blood mononuclear cells associated with lesion formation in this model are, in fact, monocytes, which subsequently undergo transformation into macrophage foam cells in fatty streak lesions. The absence of medial cell involvement indicates that monocytes are the major foam cell precursor in these lesions.
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M. Febbraio, N. A. Abumrad, D. P. Hajjar, K. Sharma, W. Cheng, S. F. A. Pearce, and R. L. Silverstein A Null Mutation in Murine CD36 Reveals an Important Role in Fatty Acid and Lipoprotein Metabolism J. Biol. Chem., July 2, 1999; 274(27): 19055 - 19062. [Abstract] [Full Text] [PDF]
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S. Eligini, S. Colli, F. Basso, L. Sironi, and E. Tremoli Oxidized Low Density Lipoprotein Suppresses Expression of Inducible Cyclooxygenase in Human Macrophages Arterioscler Thromb Vasc Biol, July 1, 1999; 19(7): 1719 - 1725. [Abstract] [Full Text] [PDF]
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N. Marx, G. K. Sukhova, T. Collins, P. Libby, and J. Plutzky PPAR{alpha} Activators Inhibit Cytokine-Induced Vascular Cell Adhesion Molecule-1 Expression in Human Endothelial Cells Circulation, June 22, 1999; 99(24): 3125 - 3131. [Abstract] [Full Text] [PDF]
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C. L. Ramos, Y. Huo, U. Jung, S. Ghosh, D. R. Manka, I. J. Sarembock, and K. Ley Direct Demonstration of P-Selectin– and VCAM-1–Dependent Mononuclear Cell Rolling in Early Atherosclerotic Lesions of Apolipoprotein E–Deficient Mice Circ. Res., June 11, 1999; 84(11): 1237 - 1244. [Abstract] [Full Text] [PDF]
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D. J. Lefer and D. N. Granger Monocyte Rolling in Early Atherogenesis : Vital Role in Lesion Development Circ. Res., June 11, 1999; 84(11): 1353 - 1355. [Full Text] [PDF]
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K. H. Han, K. O. Han, S. R. Green, and O. Quehenberger Expression of the monocyte chemoattractant protein-1 receptor CCR2 is increased in hypercholesterolemia: differential effects of plasma lipoproteins on monocyte function J. Lipid Res., June 1, 1999; 40(6): 1053 - 1063. [Abstract] [Full Text]
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 P. G. Lysko, J. Weinstock, C. L. Webb, M. E. Brawner, and N. A. Elshourbagy Identification of a Small-Molecule, Nonpeptide Macrophage Scavenger Receptor Antagonist J. Pharmacol. Exp. Ther., June 1, 1999; 289(3): 1277 - 1285. [Abstract] [Full Text]
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R. J. Aiello, P.-A. K. Bourassa, S. Lindsey, W. Weng, E. Natoli, B. J. Rollins, and P. M. Milos Monocyte Chemoattractant Protein-1 Accelerates Atherosclerosis in Apolipoprotein E-Deficient Mice Arterioscler Thromb Vasc Biol, June 1, 1999; 19(6): 1518 - 1525. [Abstract] [Full Text] [PDF]
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S. C. Whitman, S. L. Hazen, D. B. Miller, R. A. Hegele, J. W. Heinecke, and M. W. Huff Modification of Type III VLDL, Their Remnants, and VLDL From ApoE-Knockout Mice by p-Hydroxyphenylacetaldehyde, a Product of Myeloperoxidase Activity, Causes Marked Cholesteryl Ester Accumulation in Macrophages Arterioscler Thromb Vasc Biol, May 1, 1999; 19(5): 1238 - 1249. [Abstract] [Full Text] [PDF]
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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]
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P. T. Shih, M.-L. Brennan, D. K. Vora, M. C. Territo, D. Strahl, M. J. Elices, A. J. Lusis, and J. A. Berliner Blocking Very Late Antigen-4 Integrin Decreases Leukocyte Entry and Fatty Streak Formation in Mice Fed an Atherogenic Diet Circ. Res., February 19, 1999; 84(3): 345 - 351. [Abstract] [Full Text] [PDF]
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G. A. Truskey, R. A. Herrmann, J. Kait, and K. M. Barber Focal Increases in Vascular Cell Adhesion Molecule-1 and Intimal Macrophages at Atherosclerosis-Susceptible Sites in the Rabbit Aorta After Short-Term Cholesterol Feeding Arterioscler Thromb Vasc Biol, February 1, 1999; 19(2): 393 - 401. [Abstract] [Full Text] [PDF]
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Y. Fujioka, A. D. Cooper, and L. G. Fong Multiple processes are involved in the uptake of chylomicron remnants by mouse peritoneal macrophages J. Lipid Res., December 1, 1998; 39(12): 2339 - 2349. [Abstract] [Full Text]
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X.-L. Chen, P. E. Tummala, M. T. Olbrych, R. W. Alexander, and R. M. Medford Angiotensin II Induces Monocyte Chemoattractant Protein-1 Gene Expression in Rat Vascular Smooth Muscle Cells Circ. Res., November 2, 1998; 83(9): 952 - 959. [Abstract] [Full Text] [PDF]
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P. Holvoet, J. Vanhaecke, S. Janssens, F. Van de Werf, and D. Collen Oxidized LDL and Malondialdehyde-Modified LDL in Patients With Acute Coronary Syndromes and Stable Coronary Artery Disease Circulation, October 13, 1998; 98(15): 1487 - 1494. [Abstract] [Full Text] [PDF]
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K. J. Moore, R. P. Fabunmi, L. P. Andersson, and M. W. Freeman In Vitro–Differentiated Embryonic Stem Cell Macrophages : A Model System for Studying Atherosclerosis-Associated Macrophage Functions Arterioscler Thromb Vasc Biol, October 1, 1998; 18(10): 1647 - 1654. [Abstract] [Full Text] [PDF]
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T. Nakagawa, S. Nozaki, M. Nishida, J. M. Yakub, Y. Tomiyama, A. Nakata, K. Matsumoto, T. Funahashi, K. Kameda-Takemura, Y. Kurata, et al. Oxidized LDL Increases and Interferon-{gamma} Decreases Expression of CD36 in Human Monocyte–Derived Macrophages Arterioscler Thromb Vasc Biol, August 1, 1998; 18(8): 1350 - 1357. [Abstract] [Full Text] [PDF]
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G. Mozes, T. Mohacsi, P. Gloviczki, S. Menawat, I. Kullo, D. Spector, J. Taylor, T. B. Crotty, and T. O'Brien Adenovirus-Mediated Gene Transfer of Macrophage Colony Stimulating Factor to the Arterial Wall In Vivo Arterioscler Thromb Vasc Biol, July 1, 1998; 18(7): 1157 - 1163. [Abstract] [Full Text] [PDF]
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S. C. Whitman, C. G. Sawyez, D. B. Miller, B. M. Wolfe, and M. W. Huff Oxidized type IV hypertriglyceridemic VLDL-remnants cause greater macrophage cholesteryl ester accumulation than oxidized LDL J. Lipid Res., May 1, 1998; 39(5): 1008 - 1020. [Abstract] [Full Text]
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Y. Nakashima, E. W. Raines, A. S. Plump, J. L. Breslow, and R. Ross Upregulation of VCAM-1 and ICAM-1 at Atherosclerosis-Prone Sites on the Endothelium in the ApoE-Deficient Mouse Arterioscler Thromb Vasc Biol, May 1, 1998; 18(5): 842 - 851. [Abstract] [Full Text] [PDF]
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S. Takami, S. Yamashita, S. Kihara, M. Ishigami, K. Takemura, N. Kume, T. Kita, and Y. Matsuzawa Lipoprotein(a) Enhances the Expression of Intercellular Adhesion Molecule-1 in Cultured Human Umbilical Vein Endothelial Cells Circulation, March 3, 1998; 97(8): 721 - 728. [Abstract] [Full Text] [PDF]
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J. S. Martens, N. E. Reiner, P. Herrera-Velit, and U. P. Steinbrecher Phosphatidylinositol 3-Kinase Is Involved in the Induction of Macrophage Growth by Oxidized Low Density Lipoprotein J. Biol. Chem., February 27, 1998; 273(9): 4915 - 4920. [Abstract] [Full Text] [PDF]
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S. K. Gupta, P. G. Lysko, K. Pillarisetti, E. Ohlstein, and J. M. Stadel Chemokine Receptors in Human Endothelial Cells. FUNCTIONAL EXPRESSION OF CXCR4 AND ITS TRANSCRIPTIONAL REGULATION BY INFLAMMATORY CYTOKINES J. Biol. Chem., February 13, 1998; 273(7): 4282 - 4287. [Abstract] [Full Text] [PDF]
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N. Nishimura, M. Harada-Shiba, S. Tajima, R. Sugano, T. Yamamura, Q. Z. Qiang, and A. Yamamoto Acquisition of Secretion of Transforming Growth Factor-beta 1 Leads to Autonomous Suppression of Scavenger Receptor Activity in a Monocyte-Macrophage Cell Line, THP-1 J. Biol. Chem., January 16, 1998; 273(3): 1562 - 1567. [Abstract] [Full Text] [PDF]
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S. S. Patel, R. Thiagarajan, J. T. Willerson, and E. T. H. Yeh Inhibition of {alpha}4 Integrin and ICAM-1 Markedly Attenuate Macrophage Homing to Atherosclerotic Plaques in ApoE-Deficient Mice Circulation, January 13, 1998; 97(1): 75 - 81. [Abstract] [Full Text] [PDF]
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H. Funayama, U. Ikeda, M. Takahashi, Y. Sakata, S.-I. Kitagawa, Y.-I. Takahashi, J.-I. Masuyama, Y. Furukawa, Y. Miura, S. Kano, et al. Human monocyte-endothelial cell interaction induces platelet-derived growth factor expression Cardiovasc Res, January 1, 1998; 37(1): 216 - 224. [Abstract] [Full Text] [PDF]
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S.-J. Hwang, C. M. Ballantyne, A. R. Sharrett, L. C. Smith, C. E. Davis, A. M. Gotto Jr, and E. Boerwinkle Circulating Adhesion Molecules VCAM-1, ICAM-1, and E-selectin in Carotid Atherosclerosis and Incident Coronary Heart Disease Cases : The Atherosclerosis Risk In Communities (ARIC) Study Circulation, December 16, 1997; 96(12): 4219 - 4225. [Abstract] [Full Text]
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K. Reue, R. D. Cohen, and M. C. Schotz Evidence for Hormone-Sensitive Lipase mRNA Expression in Human Monocyte/Macrophages Arterioscler Thromb Vasc Biol, December 1, 1997; 17(12): 3428 - 3432. [Abstract] [Full Text]
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