Impact of high-fat diet on antioxidant status, vascular wall thickening and cardiac function in adult female LDLR^–/– mice

Stéphanie Delemasure, Carole Richard, Ségolène Gambert, Jean-Claude Guilland, Catherine Vergely, Patrick Dutartre, Luc Rochette, Jean-Louis Connat

Biochemistry Department, University Hospital, Dijon, France.
COHIRO Biotechnology, Faculty of Medicine, Dijon, France.
Laboratory of Cardio-Metabolic Pathophysiology and Pharmacology, Faculty of Medicine, University of Burgundy, Inserm UMR866, Dijon, France.

DOI: 10.4236/wjcd.2012.23031                

Abstract

Background: Western diet, rich in saturated fatty acids and cholesterol, is associated with increased cardiovascular risk. We thus investigated in female mice the influence of this diet on plasma antioxidant status, vascular wall thickening and cardiac function. Methods and Results: Adult female C57BL/6J wild type (WT) and LDLR^–/– mice were fed a normal diet (ND) or a high-fat diet (HFD) for 17 weeks. HFD induced an increase in plasma lipids and vitamin C (Vit C) levels in both groups but at a much higher level in LDLR^–/– and a decrease in plasma ascorbyl free radical levels to Vit C ratio (an endogenous oxidative stress index) in LDLR^–/–. We only found a slight decrease in circulating antioxidant status evaluated by the Oxygen Radical Absorbance Capacity (ORAC) assay in WT, but not in LDLR^–/–. Echocardiography evidenced an increase in arterial wall thickness in aortic arch at atherosclerosis predilection sites in HFD LDLR^–/– as compared to ND LDLR^–/– and HFD WT. This result was confirmed by histology. Further-more, histological examination of aortic valves showed an increase in atherosclerotic lesions. Our study, using echocardiography, show that chronic HFD does not induce any major modifications of systolic function in the both mice groups. Conclusions: High-fat intake in mice causes serious disturbances in lipid plasma levels associated to variations of circulating antioxidant status due, at least in part, to an increase in Vit C. At this stage, atherosclerotic lesions, observed in aortic arch and valve, do not impair cardiac function in HFD-fed mice.

Keywords

Ascorbyl Free Radical; Echocardiography; Vitamin C; High-Fat Diet; Oxygen Radical Absorbance Capacity; Oxidant/Antioxidant Status; Systolic Function; Aortic Arch

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Damjanovic, M. and Barton, M. (2008) Fat intake and cardiovascular response. Current Hypertension Reports, 10, 25-31. doi:10.1007/s11906-008-0007-0
[2]	Ishibashi, S., Brown, M.S., Goldstein, J.L., et al. (1993) Hypercholesterolemia in low density lipoprotein receptor knockout mice and its reversal by adenovirus-mediated gene delivery. Journal of Clinical Investigation, 92, 883- 893. doi:10.1172/JCI116663
[3]	Ishibashi, S., Goldstein, J.L., Brown, M.S., et al. (1994) Massive xanthomatosis and atherosclerosis in cholesterol-fed low density lipoprotein receptor-negative mice. Journal of Clinical Investigation, 93, 1885-1893. doi:10.1172/JCI117179
[4]	Hansson, G.K. (2005) Inflammation, atherosclerosis, and coronary artery disease. The New England Journal of Medicine, 352, 1685-1695. doi:10.1056/NEJMra043430
[5]	Zhu, X., Zhang, W., Pang, X., et al. (2011) Hypolipi- demic effect of n-butanol extract from Asparagus officinalis L. in mice fed a high-fat diet. Phytotherapy Research, 25, 1119-1124. doi:10.1002/ptr.3380
[6]	Azuma, T., Tomofuji, T., Endo, Y., et al. (2011) Effects of exercise training on gingival oxidative stress in obese rats. Archives of Oral Biology, 56, 768-774. doi:10.1016/j.archoralbio.2011.01.008
[7]	Ruggiero, C., Ehrenshaft, M., Cleland, E., et al. (2011) High-fat diet induces an initial adaptation of mitochondrial bioenergetics in the kidney despite evident oxidative stress and mitochondrial ROS production. American Journal of Physiology—Endocrinology and Metabolism, 300, E1047-E1058. doi:10.1152/ajpendo.00666.2010
[8]	Salvati, S., Attorri, L., Di Benedetto, R., et al. (2011) Micronutrient-enriched rapeseed oils improve the brain oxidant/antioxidant system in rats fed a high-fat diet. Journal of Agricultural and Food Chemistry, 59, 4483- 4488. doi:10.1021/jf1042807
[9]	Hogan, S., Canning, C, Sun, S., et al. (2011) Dietary supplementation of grape skin extract improves glycemia and inflammation in diet-induced obese mice fed a western high fat diet. Journal of Agricultural and Food Chemistry, 59, 3035-3041. doi:10.1021/jf1042773
[10]	Gan, L.M., Gronros, J., Hagg, U., et al. (2007) Non-invasive real-time imaging of atherosclerosis in mice using ultrasound biomicroscopy. Atherosclerosis, 190, 313-320. doi:10.1016/j.atherosclerosis.2006.03.035
[11]	Lauzier, B., Delemasure, S., Pesant, M., Collin, B., Duvillard, L., Vergely, C., Connat, J.-L. and Rochette, L. (2009) A cholesterol-rich diet improves resistance to ischemic insult in mouse hearts but suppresses the beneficial effect of post-conditioning. Journal of Heart and Lung Transplantation, 28, 821-826. doi:10.1016/j.healun.2009.04.030
[12]	Boisvert, W.A., Spangenberg, J. and Curtiss, L.K. (1997) Role of leukocyte-specific LDL receptors on plasma lipoprotein cholesterol and atherosclerosis in mice. Arteriosclerosis, Thrombosis, and Vascular Biology, 17, 340- 347. doi:10.1161/01.ATV.17.2.340
[13]	Rottman, J.N., Ni, G. and Brown, M. (2007) Echocardiographic evaluation of ventricular function in mice. Echocardiography, 24, 83-89. doi:10.1111/j.1540-8175.2006.00356.x
[14]	Gronros, J., Wikstrom, J., Brandt-Eliasson, U., et al. (2008) Effects of rosuvastatin on cardiovascular morphology and function in an ApoE-knockout mouse model of atherosclerosis. American Journal of Physiology— Heart and Circulatory Physiology, 295, H2046-H2053. doi:10.1152/ajpheart.00133.2008
[15]	Schiller, N.B., Shah, P.M., Crawford, M., et al. () Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. Journal of the American Society of Echocardio-graphy, 2, 358-367.
[16]	Evangelista, A., Flachskampf, F.A., Erbel, R., et al. (2010) Echocardiography in aortic diseases: EAE recommendations for clinical practice. European Journal of Echocar-diography, 11, 645-658. doi:10.1093/ejechocard/jeq056
[17]	Teichholz, L.E., Kreulen, T., Herman, M.V., et al. (1976) Problems in echocardiographic volume determinations: Echocardiographic-angiographic correlations in the presence of absence of asynergy. American Journal of Cardiology, 37, 7-11. doi:10.1016/0002-9149(76)90491-4
[18]	Tessier, F., Birlouez-Aragon, I., Tjani, C., et al. (1996) Validation of a micromethod for determining oxidized and reduced vitamin C in plasma by HPLC-fluorescence. International Journal for Vitamin and Nutrition Research, 66, 166-170.
[19]	Richard, C., Lauzier, B., Delemasure, S., et al. (2008) Effects of angiotensin-1 converting enzyme inhibition on oxidative stress and bradykinin receptor expression dur- ing doxorubicin-induced cardiomyopathy in rats. Journal of Cardiovascular Pharmacology, 52, 278-285. doi:10.1097/FJC.0b013e3181865f28
[20]	Cao, G., Alessio, H.M. and Cutler, R.G. (1993) Oxygen- radical absorbance capacity assay for antioxidants. Free Radical Biology and Medicine, 14, 303-311. doi:10.1016/0891-5849(93)90027-R
[21]	Barter, P.J., Nicholls, S., Rye, K.A., et al. (2004) Antiinflammatory properties of HDL. Circulation Research, 95, 764-772. doi:10.1161/01.RES.0000146094.59640.13
[22]	Podrez, E.A. (2010) Anti-oxidant properties of high-density lipoprotein and atherosclerosis. Clinical and Experimental Pharmacology and Physiology, 37, 719-725. doi:10.1111/j.1440-1681.2010.05380.x
[23]	Bursill, C.A., Castro, M.L., Beattie, D.T., et al. (2010) High-density lipoproteins suppress chemokines and chemokine receptors in vitro and in vivo. Arteriosclerosis, Thrombosis, and Vascular Biology, 30, 1773-1778. doi:10.1161/ATVBAHA.110.211342
[24]	Millan, J., Pinto, X., Munoz, A., et al. (2009) Lipoprotein ratios: Physiological significance and clinical usefulness in cardiovascular prevention. Journal of Vascular Health and Risk Management, 5, 757-765.
[25]	Farbstein, D., Kozak-Blickstein, A. and Levy, A.P. (2010) Antioxidant vitamins and their use in preventing cardiovascular disease. Molecules, 15, 8098-8110. doi:10.3390/molecules15118098
[26]	Nakata, Y. and Maeda, N. (2002) Vulnerable atheroscle-rotic plaque morphology in apolipoprotein E-deficient mice unable to make ascorbic Acid. Circulation, 105, 1485-1490. doi:10.1161/01.CIR.0000012142.69612.25
[27]	Buettner, G.R. and Jurkiewicz, B.A. (1993) Ascorbate free radical as a marker of oxidative stress: An EPR study. Free Radical Biology and Medicine, 14, 49-55. doi:10.1016/0891-5849(93)90508-R
[28]	Retsky, K.L., Freeman, M.W. and Frei, B. (1993) Ascorbic acid oxidation product(s) protect human low density lipoprotein against atherogenic modification. Anti-rather than prooxidant activity of vitamin C in the presence of transition metal ions. Journal of Biological Chemistry, 268, 1304-1309.
[29]	Siow, R.C., Sato, H., Leake, D.S., et al. (1999) Induction of antioxidant stress proteins in vascular endothelial and smooth muscle cells: Protective action of vitamin C against atherogenic lipoproteins. Free Radical Research, 31, 309-318. doi:10.1080/10715769900300871
[30]	Gao, X., Zhao, X.L., Zhu, Y.H. et al. (2011) Tetrame-thylpyrazine protects palmitate-induced oxidative damage and mitochondrial dysfunction in C2C12 myotubes. Life Sciences, 88, 803-809. doi:10.1016/j.lfs.2011.02.025
[31]	Ruggiero, C., Ehrenshaft, M., Cleland, E., Stadler, K. (2011) High-fat diet induces an initial adaptation of mitochondrial bioenergetics in the kidney despite evident oxidative stress and mitochondrial ROS production. American Journal of Physiology—Endocrinology and Metabolism, 300, E1047-E1058. doi:10.1152/ajpendo.00666.2010
[32]	Vial, G., Dubouchaud, H., Couturier, K., Cottet-Rousselle, C., Taleux, N., Athias, A., Galinier, A., Castteilla, L. and Leverne, X.M., (2011) Effects of a high-fat diet on energy metabolism and ROS production in rat liver. Journal of Hepatology, 54, 348-356. doi:10.1016/j.jhep.2010.06.044
[33]	VanderLaan, P.A., Reardon, C.A., Getz, G.S., et al. (2004) Site specificity of atherosclerosis: Site-selective responses to atherosclerotic modulators. Arteriosclerosis, Th- rombosis, and Vascular Biology, 24, 12-22. doi:10.1161/01.ATV.0000105054.43931.f0
[34]	Li, H.Y., Tanaka, K., Oeser, B., et al. (2006) Compensatory enlargement in transplant coronary artery disease: An intravascular ultrasound study. Chinese Medical Journal (English Edition), 119, 564-569.
[35]	Bertini, P.J., Parga, J.R., Chagas, A.C., et al. (2005) Compensatory enlargement of human coronary arteries identified by magnetic resonance imaging. Brazilian Journal of Medical and Biological Research, 38, 661- 667. doi:10.1590/S0100-879X2005000500002
[36]	Schoenhagen, P., Ziada, K.M., Vince, D.G., et al. (2001) Arterial remodeling and coronary artery disease: The concept of “dilated” versus “obstructive” coronary athe-rosclerosis. Journal of the American College of Cardiology, 38, 297-306. doi:10.1016/S0735-1097(01)01374-2
[37]	Bjorkbacka, H., Kunjathoor, V.V., Moore, K.J., et al. (2004) Reduced atherosclerosis in MyD88-null mice links elevated serum cholesterol levels to activation of innate immunity signaling pathways. Nature Medicine, 10, 416-421. doi:10.1038/nm1008
[38]	Choi, S.E., Jang, H.J., Kang, Y., et al. (2010) Atheroscle- rosis induced by a high-fat diet is alleviated by lithium chloride via reduction of VCAM expression in ApoE-deficient mice. Vascular Pharmacology, 53, 264-272. doi:10.1016/j.vph.2010.09.004
[39]	Drolet, M.C., Roussel, E., Deshaies, Y., et al. (2006) A high fat/high carbohydrate diet induces aortic valve disease in C57BL/6J mice. Journal of the American College of Cardiology, 47, 850-855. doi:10.1016/j.jacc.2005.09.049
[40]	Nagy, A.C., Cserep, Z., Tolnay, E., et al. (2008) Early diagnosis of chemotherapy-induced cardiomyopathy: A prospective tissue Doppler imaging study. Pathology & Oncology Research, 14, 69-77. doi:10.1007/s12253-008-9013-4