Research paper| Volume 96, ISSUE 1, P43-52, September 1992

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Inheritability of atherosclerosis and the role of lipoproteins as risk factors in the development of atherosclerosis in WHHL rabbits: Risk factors related to coronary atherosclerosis are different from those related to aortic atherosclerosis

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      Inheritability of atherosclerosis and the influences of serum lipids on atherosclerosis were examined by following its progression in selectively bred WHHL rabbits. Our studies indicate (1) coronary atherosclerosis is clearly inherited from parents by offspring whereas inheritability of aortic atherosclerosis is uncertain; (2) coronary stenosis is positively correlated to serum cholesterol level, although the correlation coefficient is markedly low: in contrast, no relationship between serum lipid levels and aortic atherosclerosis was observed; (3) cholesterol-rich VLDL showed atherogenicity in aorta, but not in coronary arteries; (4) an unknown lipoprotein detected by 3.6% polyacrylamide gel electrophoresis was related to coronary atherosclerosis, although no relationship between the unknown lipoprotein and aortic atherosclerosis was observed. These findings suggest that there are two types of genetic factors involved in atherosclerosis, one of which is unique to coronary atherosclerosis whereas the other is related to only aortic atherosclerosis.


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        • Kannel W.B.
        • Castelli W.P.
        • Gordon T.
        • Mcnamara P.M.
        Serum cholesterol, lipoproteins and the risk of coronary heart disease, The Framingham Study.
        Ann. Intem. Med. 1971; 74: 1
        • Keys A.
        Coronary heart disease in seven countries.
        Circulation. 1970; 41: 1
        • Lipid Research Clinics Program
        The lipid research clinics coronary primary prevention trial results, I. Reduction in incidence of coronary heart disease.
        J. Am. Med. Assoc. 1984; 251: 351
        • Lipid Research Clinics Program
        The lipid research clinics coronary primary prevention trial results, II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering.
        J. Am. Med. Assoc. 1984; 251: 365
        • Tanzawa K.
        • Shimada Y.
        • Kuroda M.
        • Tsujita Y.
        • Arai M.
        • Watanabe Y.
        WHHL-rabbit: a low density lipoprotein receptor-deficient animal model for familial hypercholesterolemia.
        FEBS Lett. 1980; 118: 81
        • Kita T.
        • Brown M.S.
        • Watanabe Y.
        • Goldstein J.L.
        Deficiency of low density lipoprotein receptors in liver and adrenal gland of the WHHL rabbit, an animal model of familial hypercholesterolemia.
        in: 6th Edn. Proc. Natl. Acad. Sci. USA. 78. 1981: 2268
        • Shiomi M.
        • Ito T.
        • Watanabe Y.
        Increase in hepatic low density lipoprotein receptor activity during pregnancy in Watanabe heritable hyperlipidemic (WHHL) rabbits, an animal model for familial hypercholesterolemia.
        Biochim. Biophys. Acta. 1987; 917: 92
        • Watanabe Y.
        Serial inbreeding of rabbits with hereditary hyperlipidemia (WHHL rabbit): incidence and development of atherosclerosis and xanthoma.
        Atherosclerosis. 1980; 36: 261
        • Buja L.M.
        • Kita T.
        • Goldstein J.L.
        • Watanabe Y.
        • Brown M.S.
        Cellular pathology of progressive atherosclerosis in the WHHL rabbit, an animal model of familial hypercholesterolemia.
        Arteriosclerosis. 1983; 3: 87
        • Watanabe Y.
        • Ito T.
        • Shiomi M.
        The effect of selective breeding in the development of coronary atherosclerosis in WHHL rabbits, an animal model for familial hypercholesterolemia.
        Atherosclerosis. 1985; 56: 71
        • Watanabe Y.
        • Ito T.
        • Shiomi M.
        • Tsujita Y.
        • Kuroda M.
        • Arai M.
        • Fukami M.
        • Tamura A.
        Preventive effect of pravastatin sodium, a potent inhibitor of 3 hydroxy-3-methylglutaryl coenzyme A reductase, on coronary atherosclerosis and xanthoma in WHHL rabbits.
        Biochim. Biophys. Acta. 1988; 960: 294
        • Watanabe Y.
        • Ito T.
        • Shiomi M.
        • Tsujita Y.
        • Kuroda M.
        • Arai M.
        • Fukami M.
        • Fukusige J.
        • Tamura A.
        Suppression of established atherosclerosis and xanthomas in mature WHHL rabbits by keeping their serum cholesterol levels extremely low: effect of pravastatin sodium in combination with cholestyramine.
        Atherosclerosis. 1990; 83: 69
        • Keohane S.G.
        • Adams C.W.M.
        • Poston R.N.
        Coronary arterial dimensions and cell populations in ageing man.
        Atherosclerosis. 1988; 69: 103
        • Pesonen E.
        • Martimo P.
        • Eng D.
        • Rapola J.
        Histometry of the arterial wall: a new technique with the aid of automatic data processing.
        Lab.Invest. 1974; 30: 550
        • Hatch F.T.
        • Lees R.S.
        Practical methods for plasma lipoprotein analysis.
        Adv. Lipid Res. 1968; 6: 1
        • Narayan K.A.
        • Narayan S.
        • Kummerow R.A.
        Disc electrophoresis of human serum lipoproteins.
        Nature. 1965; 205: 246
        • Wakasugi T.
        • Mabuchi H.
        • Sakai Y.
        • Sakai T.
        • Yoshimura A.
        • Watanabe A.
        • Koizumi J.
        • Miyamoto S.
        • Takeda R.
        • Watanabe Y.
        ApoVLDL of the Watanabe heritable hyperlipidemic rabbit and cholesterol-fed rabbit.
        J. Lipid Res. 1984; 25: 246
        • Kita T.
        • Yokode M.
        • Watanabe Y.
        • Narumiya S.
        • Kawai C.
        Stimulation of cholesteryl ester synthesis in mouse peritoneal macrophages by cholesterol-rich very low density lipoproteins from the Watanabe heritable hyperlipidemic rabbit, an animal model of familial hypercholesterolemia.
        J. Clin. Invest. 1986; 77: 1460
        • Ishii K.
        • Kita T.
        • Yokode M.
        • Kume N.
        • Nagano Y.
        • Otani H.
        • Yamamura T.
        • Murayama S.
        • Morimoto Y.
        • Teranishi Y.
        • Kawai C.
        Characterization of very low density lipoprotein from Watanabe heritable hyperlipidemic rabbits.
        J. Lipid Res. 1989; 30: 1
        • Innerarity T.L.
        • Arnold K.S.
        • Weisgraber K.H.
        • Mahley R.W.
        Apolipoprotein E is the determinant that mediates the receptor uptake of β-very low density lipoprotein by mouse macrophages.
        Arteriosclerosis. 1986; 6: 114
        • Bates S.R.
        • Coughlin B.A.
        • Mazzon T.
        • Borensztajn J.
        • Getz G.S.
        Apolipoprotein E mediates the interaction of β-VLDL with macrophages.
        J. Lipid Res. 1987; 28: 787
        • Kimura J.
        • Nakagami K.
        • Amanum K.
        • Ohkuma S.
        • Yoshida Y.
        • Takano T.
        Monoclonal antibodies recognizing lipid-laden cells and extra cellular regions with lipid-laden cells in atherosclerotic aorta.
        Virchows Arch. A. 1986; 410: 159
        • Haberland M.E.
        • Fong D.
        • Cheng L.
        Malondialdehyde-altered protein occurs in atheroma of Watanabe heritable hyperlipidemic rabbits.
        Science. 1988; 241: 215
        • Palinski W.
        • Rosenfeld M.E.
        • Yla-Herttuala S.
        • Gurtner G.C.
        • Socher S.S.
        • Bulter S.W.
        • Parthasarathy S.
        • Carew T.E.
        • Steinberg D.
        • Witztum J.L.
        Low densi ty lipoprotein undergoes oxidative modification in vivo.
        in: 6th Edn. Proc. Natl. Acad. Sci. USA. 86. 1989: 1372