Resveratrol in cholesterol metabolism and atherosclerosis

Journal of Medicinal Food

Volumn 15, Issue 9, 2012, Pages 763-773

  Voloshyna, Iryna ^a   Hussaini, Syed M ^a   Reiss, Allison B ^a  

^a WINTHROP UNIVERSITY HOSPITAL   (United States)

Author keywords

antioxidant activity; cardiovascular damage; cholesterol; lipid metabolism; resveratrol

Indexed keywords

ABC TRANSPORTER A1; ABC TRANSPORTER G1; APOLIPOPROTEIN E; CASPASE 3; CASPASE 8; CASPASE 9; CHOLESTANETRIOL 26 MONOOXYGENASE; ENDOTHELIAL NITRIC OXIDE SYNTHASE; GAMMA INTERFERON; HIGH DENSITY LIPOPROTEIN; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; LIVER X RECEPTOR ALPHA; MESSENGER RNA; MITOGEN ACTIVATED PROTEIN KINASE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PLACEBO; RESVERATROL; SIRTUIN 1;

ANGIOGENESIS; ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; ATHEROSCLEROSIS; CHEMICAL STRUCTURE; CHOLESTEROL METABOLISM; CHOLESTEROL TRANSPORT; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG EXCRETION; DRUG HALF LIFE; DRUG SAFETY; DRUG TOLERABILITY; ENDOTHELIAL DYSFUNCTION; ENVIRONMENTAL STRESS; ENZYME ACTIVATION; GENE OVEREXPRESSION; GLUCOSE HOMEOSTASIS; GLUCOSE TOLERANCE; HEART INFARCTION; HEART PROTECTION; HUMAN; HYDROXYLATION; INSULIN SENSITIVITY; ISCHEMIC HEART DISEASE; LIPID METABOLISM; LIPOPROTEIN METABOLISM; LONGEVITY; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN EXPRESSION; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; THROMBOCYTE AGGREGATION; VASODILATATION;

ANGIOGENESIS MODULATING AGENTS; ANIMALS; ANTIOXIDANTS; ATHEROSCLEROSIS; CARDIOTONIC AGENTS; CHOLESTEROL; DIETARY SUPPLEMENTS; HUMANS; STILBENES; VASODILATOR AGENTS;

EID: 84865695838     PISSN: 1096620X     EISSN: 15577600     Source Type: Journal    
DOI: 10.1089/jmf.2012.0025     Document Type: Review

References (123)

1. Ferrie'res J: The French Paradox: lessons for other countries. Heart 2004;90:107-111.
2. Gronbaek M, Tjonneland A, Johnsen D, Strip C, Overvad K: Type of alcohol and drinking pattern in 56, 970 Danish men and women. Eur J Clin Nutr 2000;54:174-176. (Pubitemid 30162890)
3. Siemann EH, Creasy LL: Concentration of the phytoalexin resveratrol in wine. Am J Enol Vitic 1992;43:49-52.
4. Baur JA, Sinclair DA: Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov 2006;5:493-506. (Pubitemid 44136961)
5. Leiro J, Alvarez E, Arranz JA, Laguna R, Uriarte E, Orallo F: Effects of cis-resveratrol on inflammatory murine macrophages: antioxidant activity and down-regulation of inflammatory genes. J Leukoc Biol 2004;75:1156-1165. (Pubitemid 38720660)
6. Zou J, Huang Y, Cao K, Yang G, Yin H, Len J, Hsieh TC, Wu JM: Effect of resveratrol on intimal hyperplasia after endothelial denudation in an experimental rabbit model. Life Sci 2000; 68:153-163.
7. Burns J, Yokota T, Ashihara H, Lean M, Crozier A: Plant foods and herbal sources of resveratrol. J Agric Food Chem 2002;50: 3337-3340. (Pubitemid 34533643)
8. Mikulski D, Gorniak R, Molski, M: A theoretical study of the structure-radical scavenging activity of trans-resveratrol analogues and cis-resveratrol in gas phase and water environment. Eur J Med Chem 2010;45:1015-1027.
9. Ito T, Akao Y, Tanaka T, Iinuma N, Nozawa Y, Vaticanol C: A novel resveratrol tetramer, inhibits cell growth through induction of apoptosis in cancer cell lines. Biol Pharm Bull 2002;25: 147-148.
10. Boocock DJ, Patel KR, Faust GE, Normolle DP, Marczylo TH, Crowell JA, Brenner DE, Booth TD, Gescher A, Steward WP: Quantitation of trans-resveratrol and detection of its metabolites in human plasma and urine by high performance liquid chromatography. J Chromatogr B Analyt Technol Biomed Life Sci 2007;848:182-187. (Pubitemid 46464044)
11. Brown VA, Patel KR, Viskaduraki M, Crowell JA, Perloff M., Booth TD, Vasilinin G, Sen A, Schinas AM, Piccirilli G, Brown K., Steward WP, Gescher AJ, Brenner DE: Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: safety, pharmacokinetics, and effect on the insulin-like growth factor axis. Cancer Res 2010;70:9003-9011.
12. Yu C, Shin YG, Chow A, Li Y, Kosmedar JW, Lee YS, Hirschelman WH, Pezzuto JM, Mehta RG, Van Breeman RR: Human, rat and mouse metabolism of resveratrol. Pharm Res 2002;19:1907-1914. (Pubitemid 36016041)
13. Francis GA, Annicotte JS, Auwerx J: PPAR agonists in the treatment of atherosclerosis. Curr Opin Pharmacol 2003;3:186- 191. (Pubitemid 36411244)
14. Lehrke M, Lazar MA: The many faces of PPARgamma. Cell 2005;123:993-999.
15. Majdalawieh A, Ro HS: PPARgamma1 and LXRalpha face a new regulator of macrophage cholesterol homeostasis and inflammatory responsiveness, AEBP1. Nucl Recept Signal 2010; 8:e004.
16. Joseph SB, McKilligin E, Pei L, Watson MA, Collins AR, Laffitte BA, Chen M, Noh G, Goodman J, Hagger GN, Tran J, Tippin TK, Wang X, Lusis AJ, Hsueh WA, Law RE, Collins JL, Willson TM, Tontonoz P: Synthetic LXR ligand inhibits the development of atherosclerosis in mice. Proc Natl Acad Sci USA 2002;99:7604-7609. (Pubitemid 34568738)
17. Janowski BA, Willy PJ, Devi TR, Falck JR, Mangelsdorf DJ: An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature 1996;383:728-731. (Pubitemid 26360651)
18. Voloshyna I, Reiss AB: The ABC transporters in lipid flux and atherosclerosis. Prog Lipid Res 2011;50:213-224.
19. Reiss AB, Glass AD: Atherosclerosis: immune and inflammatory aspects. J Investig Med 2006;54:123-131.
20. Babiker A, Andersson O, Lund E, Xiu R, Deeb S, Reshef A, Leitersdorf E, Diczfalusy U, Bjorkhem I: Elimination of cholesterol in macrophages and endothelial cells by the sterol 27- hydroxylase mechanism. J Biol Chem 1997;272: 26253-26261.
21. Reiss AB, Awadallah NW, Cronstein BN: Cytochrome P450 cholesterol 27-hydroxylase: an anti-atherogenic enzyme. Recent Res Dev Lipids Res 2000;4:39-50.
22. Tobin KA, Steineger HH, Alberti S, Spydevold O, Auwerx J, Gustafsson JA, Nebb HI: Crosstalk between fatty acid and cholesterol metabolism mediated by liver X receptoralpha. Mol Endocrinol 2000;14:741-752. (Pubitemid 32266072)
23. Cho IJ, Ahn JY, Kim S, Choi MS, Ha TY: Resveratrol attenuates the expression of HMG-CoA reductase mRNA in hamsters. Biochem Biophys Res Commun 2008;367:190-194.
24. Frankel EN, Waterhouse AL, Kinsella JE: Inhibition of human LDL oxidation by resveratrol. Lancet 1993;341:1103-1104. (Pubitemid 23114451)
25. Auger C, Teissedre PL, Ge'rain P, Lequeux N, Bornet A, Serisier S, Besançon P, Caporiccio B, Cristol JP, Rouanet J: Dietary wine phenolics catechin, quercetin, and resveratrol efficiently protect hypercholesterolemic hamsters against aortic fatty streak accumulation. J Agric Food Chem 2005;53:2015-2021. (Pubitemid 40395767)
26. Berrougui H, Grenier G, Loued S, Drouin G, Khalil A: A new insight into resveratrol as an atheroprotective compound: inhibition of lipid peroxidation and enhancement of cholesterol efflux. Atherosclerosis 2009;207:420-427.
27. Staels B, Fruchart JC: Therapeutic roles of peroxisome proliferator-activated receptor agonists. Diabetes 2005;54: 2460-2470. (Pubitemid 41134276)
28. Lowell BB: PPARgamma: an essential regulator of adipogenesis and modulator of fat cell function. Cell 1999;99:239-242. (Pubitemid 29519902)
29. Tontonoz P, Nagy L, Alvarez JG, et al.: PPARc promotes monocyte/macrophage differentiation and uptake of oxidized LDL. Cell 1998;93:241-252. (Pubitemid 28180857)
30. Chawla A, Boisvert WA, Lee CH, Laffitte BA, Barak Y, Joseph SB, Liao D, Nagy L, Edwards PA, Curtiss LK, Evans RM, Tontonoz P: A PPAR gamma-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis. Mol Cell 2001;7:161-171. (Pubitemid 32162909)
31. Chinetti G, Lestavel S, Bocher V, Remaley AT, Neve B, Torra IP, Teissier E, Minnich A, Jaye M, Duverger N, Brewer HB, Fruchart JC, Clavey V, Staels B: PPAR-alpha and PPARgamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway. Nat Med 2001;7:53-58. (Pubitemid 32095642)
32. Costet P, Luo Y, Wang N, Tall AR: Sterol-dependent transactivation of the ABC1 promoter by the liver X receptor/retinoid X receptor. J Biol Chem 2000;275:28240-28245.
33. Laffitte BA, Repa JJ, Joseph SB, Wilpitz DC, Kast HR, Mangelsdorf DJ, Tontonoz P: LXRs control lipid-inducible expression of the apolipoprotein E gene in macrophages and adipocytes. Proc Natl Acad Sci USA 2001;98:507-512. (Pubitemid 32105072)
34. Janowski BA, Grogan MJ, Jones SA, Wisely GB, Kliewer SA, Corey EJ, Mangelsdorf DJ: Structural requirements of ligands for the oxysterol liver X receptors LXRalpha and LXRbeta. Proc Natl Acad Sci USA 1999;96:266-271. (Pubitemid 29036088)
35. Laffitte BA, Joseph SB, Walczak R, Pei L, Wilpitz DC, Collins JL, Tontonoz P: Autoregulation of the human liver X receptor alpha promoter. Mol Cell Biol 2001;21:7558-7568. (Pubitemid 32988767)
36. Inoue H, Jiang X, Katayama T, Osada S, Umesono K, Namura S: Brain protection by resveratrol and fenofibrate against stroke requires peroxisome proliferator-activated receptor alpha in mice. Neurosci Lett 2003;352:203-206. (Pubitemid 38367603)
37. Schuler M, Ali F, Chambon C, Duteil D, Bornert JM, Tradivel A, Desvergne B, Wahli W, Chambon P, Metzger D: PGC1 alpha expression is controlled in skeletal muscles by PPARb, whose ablation results in fiber-type switching, obesity and type 2 diabetes. Cell Metab 2006;4:407-414. (Pubitemid 44645068)
38. Mandard S, Muller M, Kersten S: Peroxisome proliferator activated receptor alpha target genes. Cell Mol Life Sci 2004;61: 393-416. (Pubitemid 38316578)
39. Zolnerciks JK, Andress EJ, Nicolaou M, Linton KJ: Structure of ABC transporters. Essays Biochem 2011;50:43-61.
40. Higgins CF: ABC transporters: from microorganisms to man. Annu Rev Cell Biol 1992;8:67-113. (Pubitemid 23000992)
41. Brunham LR, Kruit JK, Iqbal J, Fievet C, Timmins JM, Pape TD, Coburn BA, Bissada N, Staels B, Groen AK, Hussain MM, Parks JS, Kuipers F, Hayden MR: Intestinal ABCA1directly contributes to HDL biogenesis in vivo. J Clin Invest 2006;116: 1052-1062.
42. Langmann T, Klucken J, Reil M, Liebisch G, Luciani MF, Chimini G, Kaminski WE, Schmitz G: Molecular cloning of the human ATP-binding cassette transporter 1 (hABC1): evidence for sterol-dependent regulation in macrophages. Biochem Biophys Res Commun 1999;257:29-33. (Pubitemid 29299042)
43. Gordon DJ, Rifkind BM: High-density lipoprotein - the clinical implications of recent studies. N Engl J Med 1989;321:1311- 1316. (Pubitemid 19267219)
44. Brooks-Wilson A, Marcil M, Clee SM, Zhang LH, Roomp K, van Dam M, Yu L, Brewer C, Collins JA, Molhuizen HO, Loubser O, Ouelette BF, Fichter K, Ashbourne-Excoffon KJ, Sensen CW, Scherer S, Mott S, Denis M, Martindale D, Frohlich J, Morgan K, Koop B, Pimstone S, Kastelein JJ, Genest J Jr, Hayden MR: Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency. Nat Genet 1999;22:336-345. (Pubitemid 29369523)
45. Oram J, Vaughan A: ATP-binding cassette cholesterol transporters and cardiovascular disease. Circ Res 2006;9:1031- 1043. (Pubitemid 44729927)
46. Wang N, Silver DL, Costet P, Tall AR: Specific binding of ApoA-I, enhanced cholesterol efflux, and altered plasma membrane morphology in cells expressing ABC1. J Biol Chem 2000;275:33053-33058.
47. Vaugham AM, Oram JF: ABCA1 redistributes membrane cholesterol independent of apolipoprotein interactions. J Lipid Res 2003;44:1373-1380. (Pubitemid 37279619)
48. Van Eck M, Singaraja RR, Ye D, Hildebrand RB, James ER, Hayden MR, Van Berkel TJ: Macrophage ATP-binding cassette transporter A1 overexpression inhibits atherosclerotic lesion progression in low-density lipoprotein receptor knockout mice. Arterioscler Thromb Vasc Biol 2006;26:929-934. (Pubitemid 43732174)
49. Ogata M, Tsujita M, Hossain MA, Akita N, Gonzalez FJ, Staels B, Suzuki S, Fukutomi T, Kimura G, Yokoyama S: On the mechanism for PPAR agonists to enhance ABCA1 gene expression. Atherosclerosis 2009;205:413-419.
50. Trasino S, Kim YS, Wang TT: Cancer preventive phytochemicals uniquely activate liver X receptor responsive genes through receptor dependent and independent mechanisms in prostate cancer cells. FASEB J 2009;23:717.
51. Sevoy M, Elfineh L, Cavelier LB: Resveratrol regulates the expression of LXR-alpha in human macrophages. Biochem Biophys Res Commun 2006;348:1047-1054. (Pubitemid 44233521)
52. Park DW, Baek K, Kim JR, Lee JJ, Ryu SH, Chin BR, Baek SH: Resveratrol inhibits foam cell formation via NADPH oxidase 1-mediated reactive oxygen species and monocyte chemotactic protein-1. Exp Mol Med 2009;41:171-179.
53. McLaren JE, Ramji DP: Interferon c: a master regulator of atherosclerosis. Cytokine Growth Factor Rev 2009;20:125-135.
54. Schroder K, Hertzog PJ, Ravasi T, Hume DA: Interferon-c: an overview of signals, mechanisms and functions. J Leukoc Biol 2004;75:163-189. (Pubitemid 38174573)
55. Fernades JL, Manomi RL, Orford JL, Garcia C, Selwyn AP, Coelho OR, Blotta MH: Increased Th1 activity in patients with coronary artery disease. Cytokine 2004; 26:131-137. (Pubitemid 38596923)
56. Igarashi K, Garotta G, Ozmen L, Ziemiecki A, Wilks AF, Harpur AG, Larner AC, Finbloom DS: Interferon-c induces tyrosine phosphorylation of interferon-c receptor and regulated association of protein tyrosine kinases, Jak1 and Jak2, with its receptor. J Biol Chem 1994;269:14333-14336.
57. Levy DE, Darnell JE: STATs: transcriptional control and biological impact. Nat Rev Mol Cell Biol 2002;3:651-662. (Pubitemid 34987786)
58. Agrawal S, Febbraio M, Podrez E, Cathcart MK, Stark GR, Chisolm GM: Signal transducer and activator of transcription 1 is required for optimal foam cell formation and atherosclerotic lesion development. Mol Cel Biol 2007;115:2939-2947. (Pubitemid 46912097)
59. Dolhain RJ, ter Haar NT, Hoefakker S, Tak PP, de Ley M, Claassen E, Breedveld FC, Miltenburg AM: Increased expression of interferon (IFN)-c together with IFN-c receptor in the rheumatoid synovial membrane compared with synovium of patients with osteoarthritis. Br J Rheumatol 1996;35:24-32.
60. Gottenberg JE, Chiocchia G: Dendritic cells and interferonmediated autoimmunity. Biochimie 2007;89:856-871.
61. Boscolo P, del Signore A, Sabbioni E, Di Gioacchino M, Di Giampaolo L, Reale M: Effects of resveratrol on lymphocyte proliferation and cytokine release. Ann Clin Lab Sci 2003;33: 226-231. (Pubitemid 36705934)
62. Gao X, Xu YX, Janakiraman N, Chapman RA, Gautam SC: Immunomodulatory activity of resveratrol: suppression of lymphocyte proliferation, development of cell-mediated cytotoxicity, and cytokine production. Biochem Pharmacol 2011;62:1299-1308.
63. Hai OY, Anwar K, Wirkowski PA, Voloshyna I, Carsons SE, Reiss AB: Resveratrol counters atherogenic effects of interferongamma on cholesterol efflux in THP1 human monocytes/ macrophages [abstract]. J Am Coll Cardiol 2010;55:A165.
64. Bordone L, Guarente L: Calorie restriction, SIRT1 and metabolism: understanding longevity. Nat Rev Mol Cell Biol 2005;6: 298-305. (Pubitemid 40516896)
65. Rodgers JT, Puigserver P: Fasting dependent glucose and lipid metabolic response through hepatic sirtuin 1. Proc Natl Acad Sci USA 2007;104:12861-12866. (Pubitemid 47255245)
66. Sun C, Zhang F, Ge X, Yan T, Chen X, Shi X, Zhai Q: SIRT1 improves insulin sensitivity under insulin resistant conditions by repressing PTP1B. Cell Metab 2007;6:307-319. (Pubitemid 47468091)
67. Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P, Elliott P, Geny B, Laakso M, Puigserver P, Auwerx J: Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 2006;127:1109-1122. (Pubitemid 44894520)
68. Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR, Frye RA, Mayo MW: Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J 2004;23:2369-2380. (Pubitemid 38954844)
69. Li X, Zhang S, Blander G, Tse JG, Krieger M, Guarente L: SIRT1 deacetylates and positively regulates the nuclear receptor LXR. Mol Cell 2007;28:91-106. (Pubitemid 47531974)
70. Stein S, Lohmann C, Schafer N, Hofmann J, Rohrer L, Besler C, Rothgiesser KM, Becher B, Hottiger MO, Bore'n J, McBurney MW, Landmesser U, Luscher TF, Matter CM: SIRT1 decreases Lox-1-mediated foam cell formation in atherogenesis. Eur Heart J 2010;31:2301-2309.
71. Stein S, Matter CM: Protective roles of SIRT1 in atherosclerosis. Cell Cycle 2011;10:640-647.
72. Mattagajasingh I, Kim CS, Naqvi A, Yamamori T, Hoffman TA, Jung SB, DeRicco J, Kasuno K, Irani K: SIRT1 promotes endothelium-dependent vascular relaxation by activating endothelial nitric oxide synthase. Proc Natl Acad Sci USA 2007; 104:14855-14860. (Pubitemid 350003232)
73. Zhang QJ, Wang Z, Chen HZ, Zhou S, Zheng W, Liu G, Wei YS, Cai H, Liu DP, Liang CC. Endothelium-specific overexpression of class III deacetylase SIRT1 decreases atherosclerosis in apolipoprotein E-deficient mice. Cardiovasc Res 2008;80:191-199.
74. Csiszar A, Labinskyy N, Pinto JT, Ballabh P, Zhang H, Losonczy G, Pearson K, de Cabo R, Pacher P, Zhang C, Ungvari Z: Resveratrol induces mitochondrial biogenesis in endothelial cells. Am J Physiol Heart Circ Physiol 2009;297: H13-H20.
75. Borra MT, Smith BC, Denu JM: Mechanism of human SIRT1 activation by resveratrol. J Biol Chem 2005;280:17187-17195. (Pubitemid 41389185)
76. Kaeberlein M, McDonagh T, Heltweg B, Hixon J, Westman EA, Caldwell SD, Napper A, Curtis R, Di Stefano PS, Fields S, Bedaloy A, Kennedy BK: Substrate specific activation of sirtuins by resveratrol. J Biol Chem 2005;280:17038- 17045. (Pubitemid 41389166)
77. Pacholec M, Bleasdale JE, Chrunyk B, Cunningham D, Flynn D, Garofalo RS, Griffith D, Griffor M, Loulakis P, Pabst B, Qiu X, Stockman B, Thanabal V, Varghese A, Ward J, Withka J, Ahn K: SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1. J Biol Chem 2010;285:8340-8351.
78. Gracia-Sancho J, Villarreal G Jr, Zhang Y, Garci'a-Cardena G: Activation of SIRT1 by resveratrol induces KLF2 expression conferring an endothelial vasoprotective phenotype. Cardiovasc Res 2010;85:514-519.
79. Rakici O, Kiziltepe U, Coskun B, Aslamaci S, Akar F: Effect of resveratrol on vascular tone and endothelial function of human saphenous vein and internal mammary artery. Int J Cardiol 2005;105: 209-215. (Pubitemid 41512489)
80. Penumathsa SV, Koneru S, Samuel SM, Maulik G, Bagchi D, Yet SF, Menon VP, Maulik N: Strategic targets to induce neovascularization by resveratrol in hypercholesterolemic rat myocardium: role of caveolin-1, endothelial nitric oxide synthase, hemeoxygenase-1, and vascular endothelial growth factor. Free Radic Biol Med 2008;45:1027-1034.
81. Robich MP, Osipov RM, Nezafat R, Feng J, Clements RT, Bianchi C, Boodhwani M, Coady MA, Laham RJ, Sellke F: Resveratrol improves myocardial perfusion in a swine model of hypercholesterolemia and chronic myocardial ischemia. Circulation 2011;122(11 Suppl):S142-S149.
82. West XZ, Malinin NL, Merkulova AA, Tischenko M, Kerr BA, Borden EC, Podrez EA, Salomon RG, Byzova TV: Oxidative stress induces angiogenesis by activating TLR2 with novel endogenous ligands. Nature 2010;467:972-976.
83. Kaga S, Zhan L, Matsumoto M, Maulik N: Resveratrol enhances neovascularization in the infarcted rat myocardium through the induction of thioredoxin-1, heme oxygenase-1 and vascular endothelial growth factor. J Mol Cell Cardiol 2005; 39:813-822. (Pubitemid 41464418)
84. Steinberg GR, Kemp BE: AMPK in health and disease. Physiol Rev 2009;89:1025-1078.
85. Misra P: AMP activated protein kinase; a next generation target for total metabolic control. Expert Opin Ther Targets 2008;12: 91-100. (Pubitemid 351247165)
86. Eli'es J, Cui'nas A, Garci'a-Morales V, Orallo F, Campos-Toimil M: Trans-resveratrol simultaneously increases cytoplasmic Ca2 + levels and nitric oxide release in human endothelial cells. Mol Nutr Food Res 2011;55:1237-1248.
87. Zang M, Xu S, Maitland-Toolan KA, Zuccollo A, Hou X, Jiang B, Wierzbicki M, Verbeuren T.J, Cohen RA: Polyphenols stimulate AMP activated protein kinase, lower lipids and inhibit accelerated atherosclerosis in diabetic LDL receptor deficient mice. Diabetes 2006;55:2180-2191. (Pubitemid 44743614)
88. Hwang JT, Kwon DY, Yoon SH: AMP-activated protein kinase: a potential target for the diseases prevention by natural occurring polyphenols. Nat Biotechnol 2009;26:17-22.
89. Um JH, Park SJ, Kang H, Yang S, Foretz M, McBurney MW, Kim MK, Viollet B, Chung JH: AMPK-deficient mice are resistant to the metabolic effects of resveratrol. Diabetes 2010;59: 554-563.
90. Xu Q, Hao X, Yang Q, Si L: Resveratrol prevents hyperglycemiainduced endothelial dysfunction via activation of adenosine monophosphate-activated protein kinase. Biochem Biophys Res Commun 2009;388:389-94.
91. Li D, Wang D, Wang Y, Ling W, Feng X, Xia M: Adenosine monophosphate-activated protein kinase induces cholesterol efflux from macrophage-derived foam cells and alleviates atherosclerosis in apolipoprotein E-deficient mice. J Biol Chem 2010;285:33499-33509.
92. Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA: Resveratrol improves health and survival of mice on a high calorie diet. Nature 2006;444:337-342.
93. Hou X, Xu S, Maitland-Toolan KA, Sato K, Jiang B, Ido Y, Lan F, Walsh K, Wierzbicki M, Verbeuren TJ, Cohen RA: SIRT1 regulates hepatocyte lipid metabolism through activating AMPactivated protein kinase. J Biol Chem 2008;283:20015-20026.
94. Vanhoutte PM, Shimokawa H, Tang EH, Feletou M: Endothelial dysfunction and vascular disease. Acta Physiol 2009; 196:193-222.
95. Heitzer T, Schlinzig T, Krohn K, Meinertz T, Munzel T: Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease. Circulation 2001;104:2673-2678. (Pubitemid 33108132)
96. d'Uscio LV, Baker TA, Mantilla CB, Smith L, Weiler D, Sieck GC, Katusic ZS: Mechanism of endothelial dysfunction in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 2001;21:1017-1022. (Pubitemid 34168662)
97. Yusuf S, Dagenais G, Pogue J, Bosch J, Sleight P: Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000;342:154-160. (Pubitemid 30051646)
98. Mitra S, Deshmukh A, Sachdeva R, Lu J, Mehta JL: Oxidized low-density lipoprotein and atherosclerosis implications in antioxidant therapy. Am J Med Sci 2011;342:135-142.
99. Chen AF, Chen DD, Daiber A, Faraci FM, Li H, Rembold CM, Laher I: Free radical biology of the cardiovascular system. Clin Sci (Lond) 2012;123:73-91.
100. Berliner JA, Heinecke JW: The role of oxidized lipoproteins in atherogenesis. Free Radic Biol Med 1996;20:707-727. (Pubitemid 26105783)
101. Marcil V, Delvin E, Sane AT, Tremblay A, Levy E: Oxidative stress influences cholesterol efflux in THP-1 macrophages: role of ATP-binding cassette A1 and nuclear factors. Cardiovasc Res 2006;72:473-482. (Pubitemid 44755054)
102. Catapano AL, Maggi FM, Tragni E: Low density lipoprotein oxidation, antioxidants and atherosclerosis. Curr Opin Cardiol 2000;15:355-363.
103. Regnstrom J, Nilsson J, Tornvall P, Landou C, Hamsten A: Susceptibility to low-density lipoprotein oxidation and coronary atherosclerosis in man. Lancet 1992;339:1183-1186.
104. Heinecke JW: Oxidants and antioxidants in the pathogenesis of atherosclerosis: implications for the oxidized low-density lipoprotein hypothesis. Atherosclerosis 1998;141:1-15. (Pubitemid 28539412)
105. Fabris S, Momo F, Ravagnan G, Stevanato R: Antioxidant properties of resveratrol and piceid on lipid peroxidation in micelles and monolamellar liposomes. Biophys Chem 2008;135: 76-83.
106. Gutie'rrez-Pe'rez A, Corte's-Rojo C, Noriega-Cisneros R, Caldero'n-Corte's E, Manzo-Avalos S, Clemente-Guerrero M, Godi'nez-Herna'ndez D, Boldogh I, Saavedra-Molina A: Protective effects of resveratrol on calcium-induced oxidative stress in rat heart mitochondria. J Bioenerg Biomembr 2011;43: 101-107.
107. Spanier G, Xu H, Xia N, Tobias S, Deng S, Woinowski L, Fostermann U, Li H: Resveratrol reduces endothelial oxidative stress by modulating the gene expression of superoxide dismutase-1, glutathione peroxidase-1 and NADPH oxidase subunit-4. Physiol Pharmacol 2009;60(Suppl 4):111-116.
108. Xia N, Daiber A, Habermeier A, Closs EI, Thum T, Spanier G, Lu Q, Oelze M, Torzewski M, Lackner KJ, Munzel T, Fo rstermann U, Li H: Resveratrol reverses endothelial nitric-oxide synthase uncoupling in apolipoprotein E knockout mice. J Pharmacol Exp Ther 2010;335:149-154.
109. Fremont L, Belguendouz L, Delpal S: Antioxidant activity of resveratrol and alcohol-free wine polyphenols related to LDL oxidation and polyunsaturated fatty acids. Life Sci 1999;64: 2511-2521. (Pubitemid 29268427)
110. Davi G, Patrono C: Platelet activation and atherothrombosis. N Engl J Med 2007;357:2482-2494.
111. Wang Z, Huang Y, Zou J, Cao K, Xu Y, Wu JM: Effects of red wine and wine polyphenol resveratrol on platelet aggregation in vivo and in vitro. Int J Mol Med 2002;9:77-79.
112. Yang Y, Wang, X, Zhang L, An H, Zao Z: Inhibitory effects of resveratrol on platelet activation induced by thromboxane A2 receptor agonist in human platelets. Am J Chin Med 2011;39: 145-159.
113. Szewczuk LM, Forti L, Stivala LA, Penning TM: Resveratrol is peroxidase mediated inactivator of COX-1 but not COX-2. A mechanistic approach to the design of COX-1 selective agents. J Biol Chem 2004;279:22727-22737. (Pubitemid 38679473)
114. William A, Hennekens CH: The role of asprin in cardiovascular disease - forgotten benefits Expert Opin Pharmacother 2004; 5:109-115. (Pubitemid 38072723)
115. Stef G, Csiszar A, Lerea K, Ungyari Z, Veress G: Resveratrol inhibits aggregation of platelets from high risk cardiac patients with aspirin resistance. J Cardiovasc Pharmacol 2006;48:1-5. (Pubitemid 44358887)
116. Lin KH, Hsiao G, Shih CM, Chou DS, Sheu JR: Mechanism of resveratrol induced platelet apoptosis. Cardiovasc Res 2009;83: 575-585.
117. Lekakis J, Rallidis LS, Andreadou I, Vamvakou G, Kazantzoglou G, Magiatis P, Skaltsounis AL, Kremastinos DT: Polyphenolic compounds from red grapes acutely improve endothelial function in patients with coronary heart disease. Eur J Cardiovasc Prev Rehabil 2005;12:596-600. (Pubitemid 44972990)
118. Wallerath T, Deckert G, Ternes T, Anderson H, Li H, Witte K, Forstermann U: Resveratrol, a polyphenolic phytoalexin present in red wine, enhances expression and activity of endothelial nitric oxide synthase. Circulation 2002;106:1652-1658.
119. Zou JG, Wang ZR, Huang YZ, Cao KJ, Wu JM: Effect of red wine and wine polyphenol resveratrol on endothelial function in hypercholesterolemic rabbits. Int J Mol Med 2003;11:317- 320.
120. Miyazaki R, Ichiki T, Hashimoto T, Inanaga K, Imayama I, Sadoshima J, Sunagawa K: SIRT1, a longevity gene, downregulates angiotensin II type 1 receptor expression in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 2008;28: 1263-1269.
121. Magyar K, Halmosi R, Palfi A, Feher G, Czopf L, Fulop A, Battyany I, Sumegi B, Toth K, Szabados E: Cardioprotection by resveratrol: a human clinical trial in patients with stable coronary artery disease. Clin Hemorheol Microcirc 2012;50: 179-87.
122. Turan B, Tuncay E, Vassort G: Resveratrol and diabetic cardiac function: focus on recent in vitro and in vivo studies. J Bioenerg Biomembr 2012;44:281-296.
123. Smoliga JM, Vang O, Baur JA: Challenges of translating basic research into therapeutics: resveratrol as an example. J Gerontol A Biol Sci Med Sci 2012;67:158-167.