Antioxidants are known to reduce cardiovascular disease by reducing the concentration of free radicals in the vessel wall and by preventing the oxidative modification of low-density lipoproteins. The prooxidative effect of a vitamin-A-deficient diet on the aorta has previously been demonstrated by us. In this study, the lipid metabolism in the aorta of rats fed on a vitamin-A-deficient diet was evaluated. Vitamin A deficiency induced a hypolipidemic effect (lower serum triglyceride and cholesterol levels) and a decreased serum paraoxonase 1/arylesterase activity. The concentrations of triglycerides, total cholesterol, free and esterified cholesterol, and phospholipids were increased in the aorta of vitamin-A-deficient rats. The phospholipid compositions showed an increase in phosphatidylcholine (PC), phosphatidylinositol plus phosphatidylserine and phosphatidylethanolamine, a decrease in sphingomyelin, and no change in phosphatidylglycerol. In the aorta, the increase in triglycerides was associated with an increased fatty acid synthesis and mRNA expression of diacylglycerol acyltransferase 1. The increased PC content was attributed to an increased synthesis, as measured by [methyl-14C]choline incorporation into PC and high CTP:phosphocholine cytidylyltransferase-α mRNA expression. The cholesterol synthesis, evaluated by [1-14C]acetate incorporated into cholesterol and mRNA expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase, did not change. The lipoprotein lipase and lectin-like oxidized low-density lipoprotein receptor 1 mRNA expression levels increased in the aorta of vitamin-A-deficient animals. The incorporation of vitamin A into the diet of vitamin-A-deficient rats reverted all the changes observed. These results indicate that a vitamin-A-deficient diet,in addition to having a prooxidative effect, alters the aorta lipid metabolism.

Keywords:
Vitamin A, Aorta, Triglycerides, Phospholipids, Cholesterol, Paraoxonase 1, Lectin-like oxidized low-density lipoprotein receptor 1
1.
West KP Jr, Howard GR, Sommer A: Vitamin A and infection: public health implications. Annu Rev Nutr 1989;9:63–86.
2.
Humphrey JH, West KP Jr, Sommer A: Vitamin A deficiency and attributable mortality among under-5-year-olds. Bull World Health Organ 1992;70:225–232.
3.
Niederreither K, Vermot J, Messaddeq N, Schuhbaur B, Chambon P, Dolle P: Embryonic retinoic acid synthesis is essential for heart morphogenesis in the mouse. Development 2001;128:1019–1031.
4.
Braunhut SJ, Palomares M: Modulation of endothelial cell shape and growth by retinoids. Microvasc Res 1991;41:47–62.
5.
Livrea MA, Tesoriere L: Antioxidant activity of vitamin A within lipid environments. Subcell Biochem 1998;30:113–143.
6.
Ahlemeyer B, Bauerbach E, Plath M, Steuber M, Heers C, Tegtmeier F, Krieglstein J: Retinoic acid reduces apoptosis and oxidative stress by preservation of SOD protein level. Free Radic Biol Med 2001;30:1067–1077.
7.
Gatica L, Alvarez S, Gomez N, Zago MP, Oteiza P, Oliveros L, Giménez MS: Vitamin A deficiency induces prooxidant environment and inflammation in rat aorta. Free Radic Res 2005;39:621–628.
8.
Shaish A, Daugherty A, O’Sullivan F, Schonfeld G, Heinecke JW: Beta-carotene inhibits atherosclerosis in hypercholesterolemic rabbits. J Clin Invest 1995;96:2075–2082.
9.
Livrea MA, Tesoriere L, Bongiorno A, Pintaudi AM, Ciaccio M, Riccio A: Contribution of vitamin A to the oxidation resistance of human low density lipoproteins. Free Radic Biol Med 1995;18:401–409.
10.
Sawamura T, Kume N, Aoyama T, Moriwaki H, Hoshikawa H, Aiba Y, Tanaka T, Miwa S, Katsura Y, Kita T, Masaki T: An endothelial receptor for oxidized low-density lipoprotein. Nature 1997;386:73–77.
11.
Kume N, Murase T, Moriwaki H, Aoyama T, Sawamura T, Masaki T, Kita T: Inducible expression of lectin-like oxidized LDL receptor-1 in vascular endothelial cells. Circ Res 1998;83:322–327.
12.
Nagase M, Hirose S, Sawamura T, Masaki T, Fujita T: Enhanced expression of endothelial oxidized low-density lipoprotein receptor (LOX-1) in hypertensive rats. Biochem Biophys Res Commun 1997;237:496–498.
13.
Pentikäinen MO, Öörni K, Kovanen PT: Lipoprotein lipase (LPL) strongly links native and oxidized low density lipoprotein particles to decorin-coated collagen: roles for both monomeric and dimeric forms of LPL. J Biol Chem 2000;275:5694–5701.
14.
Makoveichuk E, Lookene A, Olivecrona G: Mild oxidation of lipoproteins increases their affinity for surfaces covered by heparan sulfate and lipoprotein lipase. Biochem Biophys Res Commun 1998;252:703–710.
15.
Durrington PN, Mackness B, Mackness MI: Paraoxonase and atherosclerosis. Arterioscler Thromb Vasc Biol 2001;21:473–480.
16.
Tabas I: Phospholipid metabolism in cholesterol-loaded macrophages. Curr Opin Lipidol 1997;8:263–267.
17.
Diaz MN, Frei B, Vita JA, Keaney JF Jr: Antioxidants and atherosclerotic heart disease. N Engl J Med 1997;337:408–416.
18.
Reeves PG, Nielsen FH, Fahey GC Jr: AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr 1993;123:1939–1951.
19.
Bieri J, Tolliver T, Catignani G: Simultaneous determination of α-tocopherol and retinol in plasma or red cells by high pressure liquid chromatography. Am J Clin Nutr 1979;32:2143–2149.
20.
Beltowski J, Wojcicka G, Mydlarczyk M, Jamroz A: Cerivastatin modulates plasma paraoxonase/arylesterase activity and oxidant-antioxidant balance in the rat. Pol J Pharmacol 2002;54:143–150.
21.
Hara A, Radin NS: Lipid extraction of tissues with a low-toxicity solvent. Anal Biochem 1978;90:420–426.
22.
Abell LL, Levy BB, Brodie BB, Kendall FE: A simplified method for the estimation of total cholesterol in serum and demonstration of its specificity. J Biol Chem 1952;195:357–366.
23.
Rouser G, Fluster S, Yamamoto A: Two-dimensional thin-layer chromatographic separation of polar lipid and determination of phospholipids by phosphorus analysis of spots.Lipids 1970;5:494–496.
24.
Sardesai VM, Manning JA: Determination of triglycerides in plasma and tissues. Clin Chem 1968;14:156–161.
25.
Choi JW, Choi HS: The regulatory effects of thyroid hormone on the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Endocr Res 2000;26:1–21.
26.
Zhou YT, Wang ZW, Higa M, Newgard CB, Unger RH: Reversing adipocyte differentiation: implications for treatment of obesity. Proc Natl Acad Sci USA 1999;96:2391– 2395.
27.
Waterman IJ, Price NT, Zammit VA: Distinct ontogenic patterns of overt and latent DGAT activities of rat liver microsomes. J Lipid Res 2002;43:1555–1562.
28.
Kosaka H, Yoneyama H, Zhang L, Fujii S, Yamamoto A, Igarashi J: Induction of LOX-1 and iNOS expressions by ischemia-reperfusion of rat kidney and the opposing effect of L-arginine. FASEB J 2003;17:636–643.
29.
Carter JM, Waite KA, Campenot RB, Vance JE, Vance DE: Enhanced expression and activation of CTP:phosphocholine cytidylyltransferase β2 during neurite outgrowth. J Biol Chem 2003;278:44988–44994.
30.
Gerber LE, Erdman JW Jr: Retinoic acid and hypertriglyceridemia. Ann NY Acad Sci 1981;359:391–392.
31.
Lyons F, Laker MF, Marsden JR, Manuel R, Shuster S: Effect of oral 13-cis-retinoic acid on serum lipids. Br J Dermatol 1982;107:591–595.
32.
Liu H, Wu Z, Liu B: Effects of retinoic acid on secretion of apolipoproteins A I, A II, B100, C III and E by cultured HepG2 cells. Hua Xi Yi Ke Da Xue Xue Bao 2001;32:52–54.
33.
Oliver JD, Rogers MP: Effects of retinoic acid on lipoprotein lipase activity and mRNA level in vitro and in vivo. Biochem Pharmacol 1993;45:579–583.
34.
Renier G, Desfaits AC, Lambert A, Mikhail R: Role of oxidant injury on macrophage lipoprotein lipase (LPL) production and sensitivity to LPL. J Lipid Res 1996;37:799–809.
35.
Oliveros LB, Vega VA, Anzulovich AC, Ramírez DC, Giménez MS: Vitamin A deficiency modifies antioxidant defenses and essential element contents in rat heart. Nutr Res 2000;20:1139–1150.
36.
Anzulovich AC, Oliveros LB, Muñoz E, Martínez LD, Giménez MS: Nutritional deficiency alters antioxidant defenses and modifies the liver histoarchitecture in rat. J Trace Elem Exp Med 2000;13:343–357.
37.
Auerbach B, Bisgaier CL, Wölle J, Saxena U: Oxidation of low density lipoproteins greatly enhances their association with lipoprotein lipase anchored to endothelial cell matrix. J Biol Chem 1996;271:1329–1335.
38.
Finney RE, Nudelman E, White T, Bursten S, Klein P, Leer LL, Wang N, Waggoner D, Singer JW, Lewis RA: Pharmacological inhibition of phosphatidylcholine biosynthesis is associated with induction of phosphatidylinositol accumulation and cytolysis of neoplastic cell lines. Cancer Res 2000;60:5204–5213.
39.
Shiratori Y, Houweling M, Zha X, Tabas I: Stimulation of CTP:phosphocholine cytidylyltransferase by free cholesterol loading of macrophages involves signaling through protein dephosphorylation. J Biol Chem 1995;270:29894–29903.
40.
Gomez NN, Ojeda MS, Giménez MS: Lung lipid composition in zinc-deficient rats. Lipids2002;37:291–296.
41.
Kadl A, Huber J, Gruber F, Bochkov VN, Binder BR, Leitinger N: Analysis of inflammatory gene induction by oxidized phospholipids in vivo by quantitative real-time RT-PCR in comparison with effects of LPS. Vascul Pharmacol 2002;38:219–227.
42.
Kaneko T, Baba N, Matsuo M: Protective effect of phenolic antioxidants on the cytotoxicity induced by phosphatidylcholine hydroperoxide. Biosci Biotechnol Biochem 2002;64:1274–1277.
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2006
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