Abstract
We investigated whether pre-existing subendothelial smooth muscle cell (SMC) accumulations in cholesterol-fed rabbits are transformed into foam cell plaques. Twenty-four rabbits received a standard diet supplemented with 2% cholesterol for 4 or 8 weeks. Six rabbits received a supplement of 0.3% cholesterol for 35 weeks. The aorta and other systemic and pulmonary vessels were studied by immunohistochemistry for smooth muscle cells SMC (α-SMC actin), macrophages (RAM11), cell replication (proliferating cell nuclear antigen) and endothelial cells (von Willebrand factor; vWF). Initially the foam cell plaques were composed exclusively of foam cells of macrophage origin (MFC). In more advanced lesions SMC and collagen fibres were also present, leading to a fibrous transformation of the plaque. Cell replication was mainly located in the MFC. The endothelial cells covering the plaques showed an increased immunoreactivity for vWF which was also deposited in the interstitium between the FC. Pre-existing subendothelial SMC did not transform into FC. The newly formed FC plaques remained clearly separated from the pre-existing subendothelial SMC. The development of the plaques can be attributed not only to monocyte recruitment but also to macrophage multiplication.
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Anitschkow N (1913) Ueber die Veränderungen der Kaninchen aorta bei experimenteller Cholesterinsteatose. Zieglers Beitr Pathol Anat Allgem Pathol 56:379–403
Brunkwall J, Mattson E, Bergquist D (1992) Diet induced atherosclerosis in rabbits alters vascular prostacyclin release. Eicosanoids 5:197–202
Bürrig KF (1991) The endothelium of advanced arteriosclerotic plaques in humans. Arterioscler Thromb II:1678–1689
Clarkson TB, Lehner NDM, Bullock BC (1974) Specialized research applications. I. Arteriosclerosis research. In: Weisbroth SH, Flat RC, Kraus AL (eds) The biology of the laboratory rabbit, Academic Press, New York, pp 155–165
Clinton SK, Underwood R, Hayes L, Sherman ML, Kufe DW, Libby P (1992) Macrophage colony-stimulating factor gene expression in vascular cells and in experimental and human atherosclerosis. Am J Pathol 140:301–316
Clowes AW, Schwartz SM (1985) Significance of quiescent smooth muscle migration in the injured rat carotid artery. Circ Res 56:139–145
Constantinides P (1965) Experimental atherosclerosis in rabbits. In: Roberts CJ Jr, Straus R (eds) Comparative atherosclerosis, Hoeber Medical Division, New York, pp 276–290
Daoud AS, Jones R, Scott RF (1968) Dietary-induced atherosclerosis in miniature swine. II. Electron microscopy observations: characteristics of endothelial and smooth muscle cells in the proliferative lesions and elsewhere in the aorta. Exp Mol Pathol 8: 263–301
Faggiotto A, Ross R (1984) Studies of hypercholesterolemia in the nonhuman primate. I. Changes that lead to fatty streak formation. II. Fatty streak conversion to fibrous plaque. Arteriosclerosis 4: 323–356
Gerrity RG (1981) The role of the monocyte in atherogenesis. I. Transition of blood-borne monocytes into foam cells in fatty lesions. Am J Pathol 103:181–190
Guyton JR, Klemp KF (1992) Early extracellular and cellular lipid deposits in aorta of cholesterol-fed rabbits. Am J Pathol 141:925–936
Kockx MM, De Meyer GRY, Jacob WA, Bult H, Herman AG (1992) Triphasic sequence of neointimal formation in the cuffed carotid artery of the rabbit. Arterioscler Thromb 12:1447–1457
Kockx MM, Wuyts FL, Buyssens N, Van den Bossche RM, De Meyer GRY, Bult H, Herman AG (1993) Longitudinally orientated smooth muscle cells in rabbit arteries. Virchows Arch [A] 422:203–299
Kockx MM, De Meyer GRY, Andries LJ, Bult H, Jacob WA, Herman AG (1993) The endothelium during cuff induced neointima formation in the rabbit carotid artery. Arterioscler Thromb 13:1874–1884
Koletsky S, Snajdar R (1981) Atherosclerosis following balloon catheter injury to the carotid artery and the aorta of hypertensive rats with normolipidemia or hyperlipidemia. Am J Pathol 103:105–115
Omodeo Sale F, Archesini S, Fishman SH, Berra B (1984) A sensitive enzymatic assay for determination of cholesterol in lipid extracts. Anal Biochem, 142:347–350
Prior JT, Kurtz DM, Ziegler DD (1961) The hypercholesterolemic rabbit. Arch Pathol 71:81–94
Rosenfeld ME, Ross R (1990) Macrophage and smooth muscle cell proliferation in atherosclerotic lesions of WHHL and comparably hypercholesterolemic fat-fed rabbits. Arteriosclerosis 10:680–687
Rosenfeld ME, Tsukada T, Gown AM, Ross R (1987) Fatty streak initiation in Watanabe heritable hyperlipemic and comparably hypercholesterolemic fat fed rabbits. Arteriosclerosis 7:9–23
Rosenfeld ME, Yla-Herttuala S, Lipton BA, Ord VA, Witztum JL, Steinberg D (1992) Macrophage colony-stimulating factor mRNA and protein in atherosclerotic lesions of rabbits and humans. Am J Pathol 140:291–300
Ross R (1993) The pathogenesis of atherosclerosis: a perspective for the 1990's. Nature 362:801–809
Stary HC (1992) Composition and classification of human atherosclerotic lesions. Virchows Archiv [A] 421:277–290
Still WJS (1964) Pathogenesis of experimental atherosclerosis. Arch Pathol 78:601–612
Taylor KE, Glagov S, Zarins CK (1989) Preservation and structural adaptation of endothelium over experimental foam cell lesions. Arteriosclerosis, 9:881–894
Trillo AA, Prichard RW (1979) Early endothelial changes in experimental primate arteriosclerosis. Lab Invest 41:294–302
Wilson RB, Miller RA, Middleton CC, Kinden D (1982) Atherosclerosis in rabbits fed a low cholesterol diet for five years. Arteriosclerosis 2:228–241
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Kockx, M.M., Buyssens, N., Van den Bossche, R. et al. The relationship between pre-existing subendothelial smooth muscle cell accumulations and foam cell lesions in cholesterol-fed rabbits. Vichows Archiv A Pathol Anat 425, 41–47 (1994). https://doi.org/10.1007/BF00193947
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DOI: https://doi.org/10.1007/BF00193947