Biopolym. Cell. 2008; 24(1):78-81.
Short Communications
Influence of human apolipoprotein A-1 transgene injection on level of cholesterol and morphology of tissues of rabbits on cholesterol diet
1Gilchuk Iu. M., 1Toporova O. K., 2Novikova S. M., 1Kordium V. A.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
  2. Gerontology Institute of the Academy of Medical Sciences of Ukraine
    67, Vyshgorodska Str., Kyiv, Ukraine, 04114


It has been shown that repetitive injection of plasmid DNA, containing human apolipoprotein A-1 (apoA-1) gene, in the complex with polyethylenimine into the liver parenchyma of cholesterol-rich diet rabbits influenced cholesterol concentration in animal blood and liver and morphology of vessel tissues. Thus, apoA-1 injected animals were shown not to reveal the increase in total cholesterol concentration in blood and morphology alteration of liver and vessel tissues, specific for atherosclerosis in cholesterol-fed rabbits. The data obtained reveal that human apoA-1 transgene injection might suppress experimental atherosclerosis in cholesterol-fed rabbits.
Keywords: apolipoprotein A-1, atherosclerosis, transgene


[1] Kruth HS. Lipoprotein cholesterol and atherosclerosis. Curr Mol Med. 2001;1(6):633-53.
[2] von Eckardstein A, Nofer JR, Assmann G. High density lipoproteins and arteriosclerosis. Role of cholesterol efflux and reverse cholesterol transport. Arterioscler Thromb Vasc Biol. 2001;21(1):13-27.
[3] Gordon DJ, Rifkind BM. High-density lipoprotein--the clinical implications of recent studies. N Engl J Med. 1989;321(19):1311-6.
[4] Castelli WP, Anderson K, Wilson PW, Levy D. Lipids and risk of coronary heart disease. The Framingham Study. Ann Epidemiol. 1992;2(1-2):23-8.
[5] Criqui MH. Epidemiology of atherosclerosis: an updated overview. Am J Cardiol. 1986;57(5):18C-23C.
[6] Zemel PC, Sowers JR. Relation between lipids and atherosclerosis: epidemiologic evidence and clinical implications. Am J Cardiol. 1990;66(21):7-12.
[7] Frank PG, Marcel YL. Apolipoprotein A-I: structure-function relationships. J Lipid Res. 2000;41(6):853-72.
[8] Schaefer EJ, Heaton WH, Wetzel MG, Brewer HB Jr. Plasma apolipoprotein A-1 absence associated with a marked reduction of high density lipoproteins and premature coronary artery disease. Arteriosclerosis. 1982;2(1):16-26.
[9] The norm in medical practice: Handbook Ed.: VA Milyagin. M. MEDpress Inform 2006. 144.
[10] Nanjee MN, Crouse JR, King JM, Hovorka R, Rees SE, Carson ER, Morgenthaler JJ, Lerch P, Miller NE. Effects of intravenous infusion of lipid-free apo A-I in humans. Arterioscler Thromb Vasc Biol. 1996;16(9):1203-14.
[11] Miyazaki A, Sakuma S, Morikawa W, Takiue T, Miake F, Terano T, Sakai M, Hakamata H, Sakamoto Y, Natio M, et al. Intravenous injection of rabbit apolipoprotein A-I inhibits the progression of atherosclerosis in cholesterol-fed rabbits. Arterioscler Thromb Vasc Biol. 1995;15(11):1882-8.
[12] Brousseau ME, Hoeg JM. Transgenic rabbits as models for atherosclerosis research. J Lipid Res. 1999;40(3):365-75.
[13] Plump AS, Scott CJ, Breslow JL. Human apolipoprotein A-I gene expression increases high density lipoprotein and suppresses atherosclerosis in the apolipoprotein E-deficient mouse. Proc Natl Acad Sci U S A. 1994;91(20):9607-11.
[14] Paszty C, Maeda N, Verstuyft J, Rubin EM. Apolipoprotein AI transgene corrects apolipoprotein E deficiency-induced atherosclerosis in mice. J Clin Invest. 1994;94(2):899-903.
[15] De Geest B, Zhao Z, Collen D, Holvoet P. Effects of adenovirus-mediated human apo A-I gene transfer on neointima formation after endothelial denudation in apo E-deficient mice. Circulation. 1997;96(12):4349-56.
[16] Tangirala RK, Tsukamoto K, Chun SH, Usher D, Pur? E, Rader DJ. Regression of atherosclerosis induced by liver-directed gene transfer of apolipoprotein A-I in mice. Circulation. 1999;100(17):1816-22.
[17] Belalcazar LM, Merched A, Carr B, Oka K, Chen KH, Pastore L, Beaudet A, Chan L. Long-term stable expression of human apolipoprotein A-I mediated by helper-dependent adenovirus gene transfer inhibits atherosclerosis progression and remodels atherosclerotic plaques in a mouse model of familial hypercholesterolemia. Circulation. 2003;107(21):2726-32.
[18] Duverger N, Kruth H, Emmanuel F, Caillaud JM, Viglietta C, Castro G, Tailleux A, Fievet C, Fruchart JC, Houdebine LM, Denefle P. Inhibition of atherosclerosis development in cholesterol-fed human apolipoprotein A-I-transgenic rabbits. Circulation. 1996;94(4):713-7.
[19] Gilchuk Yu. M., Irodov D. M., Starokadomskyy P. L., Pishel I. M., Toporova O. K., Novikova S. M., Kordium V. A. The distribution of injected plasmid DNA throughout the organs and the expression of human apoA-1 gene in vivo. Biopolym. Cell. 2006; 22(6):439-445
[20] Sambrook J., Fritsch E. F., Maniatis T. Molecular cloning: a laboratory manual. New York: Cold Spring Harbor Lab. press, 1989. 625 p.
[21] Lily R. histopathological technique and practical histochemistry, New York: Wiley, 1969. 645.
[22] Moghadasian MH, Frohlich JJ, McManus BM. Advances in experimental dyslipidemia and atherosclerosis. Lab Invest. 2001;81(9):1173-83.
[23] Myasnikov AL. Atherosclerosis. M. Medgiz, 1960. 443.
[24] Tsintsiadze KI Current experimental atherosclerosis in young, mature and old rabbits. Tematicheskiy sb.: Gerontologiya i geriatriya. Tbilisi, 1981: 65–73.
[25] Novikova S. M., Toporova O. K., Likhachova L. I., Kozel YU. M., Kordyum V. A. Introduction and expression of human apoA-1 gene in liver cells of rabbits with experimental atherosclerosis. Bukovyn. med. visn. 2005; 9(2):175–177.