Int J Angiol 2012; 21(01): 007-018
DOI: 10.1055/s-0032-1306417
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Resveratrol, Wine, and Atherosclerosis

Kailash Prasad
1   Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
› Author Affiliations
Further Information

Publication History

Publication Date:
03 March 2012 (online)

Abstract

This review emphasizes the effects of resveratrol on factors involved in the mechanism of atherosclerosis and risk factors for atherosclerosis. The effects of wine and resveratrol on atherosclerosis are also discussed. Resveratrol is a potent antioxidant and an anti-inflammatory agent. It reduces the expression of cell adhesion molecules, monocyte colony stimulating factors, matrix metalloproteinases, and growth factors; and inhibits platelet aggregation and vascular smooth muscle cell proliferation. It reduces the serum levels of total cholesterol, triglycerides (TG), and raises high-density lipoprotein cholesterol, inhibits expression of C-reactive protein and lowers the levels of advanced glycation end products and its receptor in the vascular tissue. It lowers the risk factors for plaque rupture. Epidemiological data show that moderate consumption of alcohol has an inverse association with carotid atherosclerosis while high consumption has a positive association with carotid atherosclerosis. Wine reduces the extent of atherosclerosis in animal model. The antiatherosclerotic effect of wine is mainly due to it resveratrol content. Resveratrol reduces the extent of atherosclerosis in animal model of atherosclerosis (apolipoprotein [Apo] E-deficient and Apo E−/−/low-density lipoprotein receptor-deficient mice and macrophage). In rabbit model of atherosclerosis, both reduction and acceleration of atherosclerosis have been reported with resveratrol. There are no data for regression and slowing of progression of atherosclerosis. Robust clinical trials for suppression of atherosclerosis are lacking. In conclusion, resveratrol has potential but experimental studies in depth and robust clinical trials are lacking for this agent to be of any value in the primary and secondary prevention of coronary and peripheral artery disease.

 
  • References

  • 1 Statistics Canada. CAN SIM Table 102–0529: Deaths, by cause, Chapter IX: Diseases of the Circulatory System (100 to 199), age group and sex, Canada, annual (number), 2000–2006. Released May 4, 2010. Available at: http://dsp-psd.pwgsc.gc.ca/collections/collection_2010/statcan/84F0209X/8410209X2006000-eng.pdf . Accessed Jan 2012
  • 2 Rosamond AW, Flegal K, Furie K , et al. Heart Disease and Stroke Statistics 2008 Update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. [Circulation AHA web site]. December 17, 2007. Available at: http://www.circ.ahajournals.org . Accessed March 10, 2009
  • 3 Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation 1995; 92 (3) 657-671
  • 4 Nikkari ST, O'Brien KD, Ferguson M , et al. Interstitial collagenase (MMP-1) expression in human carotid atherosclerosis. Circulation 1995; 92 (6) 1393-1398
  • 5 Shah PK, Falk E, Badimon JJ , et al. Human monocyte-derived macrophages induce collagen breakdown in fibrous caps of atherosclerotic plaques. Potential role of matrix-degrading metalloproteinases and implications for plaque rupture. Circulation 1995; 92 (6) 1565-1569
  • 6 Galis ZS, Sukhova GK, Lark MW, Libby P. Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest 1994; 94 (6) 2493-2503
  • 7 Castelli WP. Cholesterol and lipids in the risk of coronary artery disease—the Framingham Heart Study. Can J Cardiol 1988; 4 (Suppl A) 5A-10A
  • 8 Ross R, Harker L. Hyperlipidemia and atherosclerosis. Science 1976; 193 (4258) 1094-1100
  • 9 Prasad K, Kalra J. Oxygen free radicals and hypercholesterolemic atherosclerosis: effect of vitamin E. Am Heart J 1993; 125 (4) 958-973
  • 10 Prasad K. Reduction of serum cholesterol and hypercholesterolemic atherosclerosis in rabbits by secoisolariciresinol diglucoside isolated from flaxseed. Circulation 1999; 99 (10) 1355-1362
  • 11 Prasad K, Kalra J, Lee P. Oxygen free radicals as a mechanism of hypercholesterolemic atherosclerosis: effects of probucol. Int J Angiol 1994; 3: 100-112
  • 12 Steinberg D. Antioxidants and atherosclerosis. A current assessment. Circulation 1991; 84 (3) 1420-1425
  • 13 Steinberg D. Antioxidants in the prevention of human atherosclerosis. Summary of the proceedings of a National Heart, Lung, and Blood Institute Workshop: September 5-6, 1991, Bethesda, Maryland. Circulation 1992; 85: 2337-2344
  • 14 Prasad K. Pathophysiology of atherosclerosis. In: Textbook of Angiology, JB Chang, R Olsen, K Prasad, BE Sumpio, eds. Springer-Verlag: New York Inc.; 2000: 85-105
  • 15 Kleemann R, Zadelaar S, Kooistra T. Cytokines and atherosclerosis: a comprehensive review of studies in mice. Cardiovasc Res 2008; 79 (3) 360-376
  • 16 Saikku P, Leinonen M, Mattila K , et al. Serological evidence of an association of a novel Chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarction. Lancet 1988; 2 (8618) 983-986
  • 17 Burke AP, Tracy RP, Kolodgie F , et al. Elevated C-reactive protein values and atherosclerosis in sudden coronary death: association with different pathologies. Circulation 2002; 105 (17) 2019-2023
  • 18 Paul A, Ko KWS, Li L , et al. C-reactive protein accelerates the progression of atherosclerosis in apolipoprotein E-deficient mice. Circulation 2004; 109 (5) 647-655
  • 19 Schmidt AM, Stern D. Atherosclerosis and diabetes: the RAGE connection. Curr Atheroscler Rep 2000; 2 (5) 430-436
  • 20 Schmidt AM, Yan SD, Wautier JL, Stern D. Activation of receptor for advanced glycation end products: a mechanism for chronic vascular dysfunction in diabetic vasculopathy and atherosclerosis. Circ Res 1999; 84 (5) 489-497
  • 21 Zhou Z, Wang K, Penn MS , et al. Receptor for AGE (RAGE) mediates neointimal formation in response to arterial injury. Circulation 2003; 107 (17) 2238-2243
  • 22 Schwartz CJ, Valente AJ, Sprague EA. A modern view of atherogenesis. Am J Cardiol 1993; 71 (6, Suppl B) 9B-14B
  • 23 Renaud S, de Lorgeril M. Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet 1992; 339 (8808) 1523-1526
  • 24 Maclure M. Demonstration of deductive meta-analysis: ethanol intake and risk of myocardial infarction. Epidemiol Rev 1993; 15 (2) 328-351
  • 25 Rimm EB, Williams P, Fosher K, Criqui M, Stampfer MJ. Moderate alcohol intake and lower risk of coronary heart disease: meta-analysis of effects on lipids and haemostatic factors. BMJ 1999; 319 (7224) 1523-1528
  • 26 Scherr PA, LaCroix AZ, Wallace RB , et al. Light to moderate alcohol consumption and mortality in the elderly. J Am Geriatr Soc 1992; 40 (7) 651-657
  • 27 Mukamal KJ, Kronmal RA, Mittleman MA , et al. Alcohol consumption and carotid atherosclerosis in older adults: the Cardiovascular Health Study. Arterioscler Thromb Vasc Biol 2003; 23 (12) 2252-2259
  • 28 Kiechl S, Willeit J, Egger G, Oberhollenzer M, Aichner F. Alcohol consumption and carotid atherosclerosis: evidence of dose-dependent atherogenic and antiatherogenic effects. Results from the Bruneck Study. Stroke 1994; 25 (8) 1593-1598
  • 29 Kauhanen J, Kaplan GA, Goldberg DE, Salonen R, Salonen JT. Pattern of alcohol drinking and progression of atherosclerosis. Arterioscler Thromb Vasc Biol 1999; 19 (12) 3001-3006
  • 30 Demirovic J, Nabulsi A, Folsom AR , et al; The Atherosclerosis Risk in Communities (ARIC) Study Investigators. Alcohol consumption and ultrasonographically assessed carotid artery wall thickness and distensibility. Circulation 1993; 88 (6) 2787-2793
  • 31 Ramprasath VR, Jones PJH. Anti-atherogenic effects of resveratrol. Eur J Clin Nutr 2010; 64 (7) 660-668
  • 32 Soleas GJ, Diamandis EP, Goldberg DM. Resveratrol: a molecule whose time has come? And gone?. Clin Biochem 1997; 30 (2) 91-113
  • 33 Romero-Pérez AI, Ibern-Gómez M, Lamuela-Raventós RM, de La Torre-Boronat MC. Piceid, the major resveratrol derivative in grape juices. J Agric Food Chem 1999; 47 (4) 1533-1536
  • 34 Orallo F, Álvarez E, Camiña M, Leiro JM, Gómez E, Fernández P. The possible implication of trans-Resveratrol in the cardioprotective effects of long-term moderate wine consumption. Mol Pharmacol 2002; 61 (2) 294-302
  • 35 Gu X, Creasy L, Kester A, Zeece M. Capillary electrophoretic determination of resveratrol in wines. J Agric Food Chem 1999; 47 (8) 3223-3227
  • 36 Burns J, Yokota T, Ashihara H, Lean MEJ, Crozier A. Plant foods and herbal sources of resveratrol. J Agric Food Chem 2002; 50 (11) 3337-3340
  • 37 Sobolev VS, Cole RJ. trans-resveratrol content in commercial peanuts and peanut products. J Agric Food Chem 1999; 47 (4) 1435-1439
  • 38 Sato M, Suzuki Y, Okuda T, Yokotsuka K. Contents of resveratrol, piceid, and their isomers in commercially available wines made from grapes cultivated in Japan. Biosci Biotechnol Biochem 1997; 61 (11) 1800-1805
  • 39 Feijóo O, Moreno A, Falqué E. Content of trans- and cis-resveratrol in Galician white and red wines. J Food Compost Anal 2008; 21: 608-613
  • 40 Ross R, Masuda J, Raines EW , et al. Localization of PDGF-B protein in macrophages in all phases of atherogenesis. Science 1990; 248 (4958) 1009-1012
  • 41 Falcone DJ, McCaffrey TA, Haimovitz-Friedman A, Vergilio JA, Nicholson AC. Macrophage and foam cell release of matrix-bound growth factors. Role of plasminogen activation. J Biol Chem 1993; 268 (16) 11951-11958
  • 42 Nilsson J, Sjölund M, Palmberg L, Thyberg J, Heldin CH. Arterial smooth muscle cells in primary culture produce a platelet-derived growth factor-like protein. Proc Natl Acad Sci U S A 1985; 82 (13) 4418-4422
  • 43 DiCorleto PE. Cultured endothelial cells produce multiple growth factors for connective tissue cells. Exp Cell Res 1984; 153 (1) 167-172
  • 44 Bowen-Pope DF, Dicorleto PE, Ross R. Interactions between the receptors for platelet-derived growth factor and epidermal growth factor. J Cell Biol 1983; 96 (3) 679-683
  • 45 Sporn MB, Roberts AB, Wakefield LM, de Crombrugghe B. Some recent advances in the chemistry and biology of transforming growth factor-beta. J Cell Biol 1987; 105 (3) 1039-1045
  • 46 Floreani M, Napoli E, Quintieri L, Palatini P. Oral administration of trans-resveratrol to guinea pigs increases cardiac DT-diaphorase and catalase activities, and protects isolated atria from menadione toxicity. Life Sci 2003; 72 (24) 2741-2750
  • 47 Jang JH, Surh YJ. Protective effects of resveratrol on hydrogen peroxide-induced apoptosis in rat pheochromocytoma (PC12) cells. Mutat Res 2001; 496 (1-2) 181-190
  • 48 Vivancos M, Moreno JJ. Effect of resveratrol, tyrosol and β-sitosterol on oxidised low-density lipoprotein-stimulated oxidative stress, arachidonic acid release and prostaglandin E2 synthesis by RAW 264.7 macrophages. Br J Nutr 2008; 99 (6) 1199-1207
  • 49 Rocha KKR, Souza GA, Ebaid GX, Seiva FRF, Cataneo AC, Novelli ELB. Resveratrol toxicity: effects on risk factors for atherosclerosis and hepatic oxidative stress in standard and high-fat diets. Food Chem Toxicol 2009; 47 (6) 1362-1367
  • 50 Li Y, Cao Z, Zhu H. Upregulation of endogenous antioxidants and phase 2 enzymes by the red wine polyphenol, resveratrol in cultured aortic smooth muscle cells leads to cytoprotection against oxidative and electrophilic stress. Pharmacol Res 2006; 53 (1) 6-15
  • 51 Cao Z, Li Y. Potent induction of cellular antioxidants and phase 2 enzymes by resveratrol in cardiomyocytes: protection against oxidative and electrophilic injury. Eur J Pharmacol 2004; 489 (1-2) 39-48
  • 52 Leonard SS, Xia C, Jiang BH , et al. Resveratrol scavenges reactive oxygen species and effects radical-induced cellular responses. Biochem Biophys Res Commun 2003; 309 (4) 1017-1026
  • 53 Soares DG, Andreazza AC, Salvador M. Sequestering ability of butylated hydroxytoluene, propyl gallate, resveratrol, and vitamins C and E against ABTS, DPPH, and hydroxyl free radicals in chemical and biological systems. J Agric Food Chem 2003; 51 (4) 1077-1080
  • 54 Vinson JA, Dabbagh YA, Serry MM, Jang J. Plant flavonoids, especially tea flavonols, are powerful antioxidants using an in vitro oxidation model for heart disease. J Agric Food Chem 1995; 43: 2800-2802
  • 55 Frankel EN, Waterhouse AL, Kinsella JE. Inhibition of human LDL oxidation by resveratrol. Lancet 1993; 341 (8852) 1103-1104
  • 56 Mizutani K, Ikeda K, Kawai Y, Yamori Y. Protective effect of resveratrol on oxidative damage in male and female stroke-prone spontaneously hypertensive rats. Clin Exp Pharmacol Physiol 2001; 28 (1-2) 55-59
  • 57 Frémont 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 (26) 2511-2521
  • 58 Juan SH, Cheng TH, Lin HC, Chu YL, Lee WS. Mechanism of concentration-dependent induction of heme oxygenase-1 by resveratrol in human aortic smooth muscle cells. Biochem Pharmacol 2005; 69 (1) 41-48
  • 59 Chow SE, Hshu YC, Wang JS, Chen JK. Resveratrol attenuates oxLDL-stimulated NADPH oxidase activity and protects endothelial cells from oxidative functional damages. J Appl Physiol 2007; 102 (4) 1520-1527
  • 60 Shigematsu S, Ishida S, Hara M , et al. Resveratrol, a red wine constituent polyphenol, prevents superoxide-dependent inflammatory responses induced by ischemia/reperfusion, platelet-activating factor, or oxidants. Free Radic Biol Med 2003; 34 (7) 810-817
  • 61 Kohnen S, Franck T, Van Antwerpen P , et al. Resveratrol inhibits the activity of equine neutrophil myeloperoxidase by a direct interaction with the enzyme. J Agric Food Chem 2007; 55 (20) 8080-8087
  • 62 Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation 2002; 105 (9) 1135-1143
  • 63 Ross R. Atherosclerosis—an inflammatory disease. N Engl J Med 1999; 340 (2) 115-126
  • 64 Leiro J, Álvarez 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 (6) 1156-1165
  • 65 MacCarrone M, Lorenzon T, Guerrieri P, Agrò AF. Resveratrol prevents apoptosis in K562 cells by inhibiting lipoxygenase and cyclooxygenase activity. Eur J Biochem 1999; 265 (1) 27-34
  • 66 Bujanda L, García-Barcina M, Gutiérrez-de Juan V , et al. Effect of resveratrol on alcohol-induced mortality and liver lesions in mice. BMC Gastroenterol 2006; 6: 35-43
  • 67 Boscolo P, del Signore A, Sabbioni E , et al. Effects of resveratrol on lymphocyte proliferation and cytokine release. Ann Clin Lab Sci 2003; 33 (2) 226-231
  • 68 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 2001; 62 (9) 1299-1308
  • 69 Gao X, Deeb D, Media J , et al. Immunomodulatory activity of resveratrol: discrepant in vitro and in vivo immunological effects. Biochem Pharmacol 2003; 66 (12) 2427-2435
  • 70 Wang MJ, Huang HM, Hsieh SJ, Jeng KCG, Kuo JS. Resveratrol inhibits interleukin-6 production in cortical mixed glial cells under hypoxia/hypoglycemia followed by reoxygenation. J Neuroimmunol 2001; 112 (1-2) 28-34
  • 71 Holmes-McNary M, Baldwin Jr AS. Chemopreventive properties of trans-resveratrol are associated with inhibition of activation of the IkappaB kinase. Cancer Res 2000; 60 (13) 3477-3483
  • 72 Shen F, Chen SJ, Dong XJ, Zhong H, Li YT, Cheng GF. Suppression of IL-8 gene transcription by resveratrol in phorbol ester treated human monocytic cells. J Asian Nat Prod Res 2003; 5 (2) 151-157
  • 73 Manna SK, Mukhopadhyay A, Aggarwal BB. Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-κ B, activator protein-1, and apoptosis: potential role of reactive oxygen intermediates and lipid peroxidation. J Immunol 2000; 164 (12) 6509-6519
  • 74 Venkatesan B, Valente AJ, Reddy VS, Siwik DA, Chandrasekar B. Resveratrol blocks interleukin-18-EMMPRIN cross-regulation and smooth muscle cell migration. Am J Physiol Heart Circ Physiol 2009; 297 (2) H874-H886
  • 75 Zhu J, Yong W, Wu X , et al. Anti-inflammatory effect of resveratrol on TNF-α-induced MCP-1 expression in adipocytes. Biochem Biophys Res Commun 2008; 369 (2) 471-477
  • 76 Cicha I, Regler M, Urschel K, Goppelt-Struebe M, Daniel WG, Garlichs CD. Resveratrol inhibits monocytic cell chemotaxis to MCP-1 and prevents spontaneous endothelial cell migration through Rho kinase-dependent mechanism. J Atheroscler Thromb 2011; 18 (12) 1031-1042
  • 77 Bertelli AA, Baccalini R, Battaglia E, Falchi M, Ferrero ME. Resveratrol inhibits TNF alpha-induced endothelial cell activation. Therapie 2001; 56 (5) 613-616
  • 78 Ahn KS, Kim JH, Oh SR, Ryu SY, Lee HK. Inhibitory activity of stilbenes from medicinal plants on the expression of cell adhesion molecules on THP1 cells. Planta Med 2000; 66 (7) 641-644
  • 79 Ferrero ME, Bertelli AE, Fulgenzi A , et al. Activity in vitro of resveratrol on granulocyte and monocyte adhesion to endothelium. Am J Clin Nutr 1998; 68 (6) 1208-1214
  • 80 Pendurthi UR, Rao LV. Resveratrol suppresses agonist-induced monocyte adhesion to cultured human endothelial cells. Thromb Res 2002; 106 (4-5) 243-248
  • 81 Carluccio MA, Siculella L, Ancora MA , et al. Olive oil and red wine antioxidant polyphenols inhibit endothelial activation: antiatherogenic properties of Mediterranean diet phytochemicals. Arterioscler Thromb Vasc Biol 2003; 23 (4) 622-629
  • 82 Ferrero ME, Bertelli AA, Pellegatta F, Fulgenzi A, Corsi MM, Bertelli A. Phytoalexin resveratrol (3-4′-5-trihydroxystilbene) modulates granulocyte and monocyte endothelial adhesion. Transplant Proc 1998; 30 (8) 4191-4193
  • 83 Leiro J, Arranz JA, Fraiz N, Sanmartín ML, Quezada E, Orallo F. Effect of cis-resveratrol on genes involved in nuclear factor kappa B signaling. Int Immunopharmacol 2005; 5 (2) 393-406
  • 84 Park DW, Baek K, Kim JR , et al. Resveratrol inhibits foam cell formation via NADPH oxidase 1- mediated reactive oxygen species and monocyte chemotactic protein-1. Exp Mol Med 2009; 41 (3) 171-179
  • 85 Araim O, Ballantyne J, Waterhouse AL, Sumpio BE. Inhibition of vascular smooth muscle cell proliferation with red wine and red wine polyphenols. J Vasc Surg 2002; 35 (6) 1226-1232
  • 86 Mnjoyan ZH, Fujise K. Profound negative regulatory effects by resveratrol on vascular smooth muscle cells: a role of p53-p21(WAF1/CIP1) pathway. Biochem Biophys Res Commun 2003; 311 (2) 546-552
  • 87 Venkatesan B, Ghosh-Choudhury N, Das F , et al. Resveratrol inhibits PDGF receptor mitogenic signaling in mesangial cells: role of PTP1B. FASEB J 2008; 22 (10) 3469-3482
  • 88 Kim JW, Lim SC, Lee MY , et al. Inhibition of neointimal formation by trans-resveratrol: role of phosphatidyl inositol 3-kinase-dependent Nrf2 activation in heme oxygenase-1 induction. Mol Nutr Food Res 2010; 54 (10) 1497-1505
  • 89 Park ES, Lim Y, Hong JT , et al. Pterostilbene, a natural dimethylated analog of resveratrol, inhibits rat aortic vascular smooth muscle cell proliferation by blocking Akt-dependent pathway. Vascul Pharmacol 2010; 53 (1-2) 61-67
  • 90 Lin MT, Yen ML, Lin CY, Kuo ML. Inhibition of vascular endothelial growth factor-induced angiogenesis by resveratrol through interruption of Src-dependent vascular endothelial cadherin tyrosine phosphorylation. Mol Pharmacol 2003; 64 (5) 1029-1036
  • 91 Uchiyama T, Toda K, Takahashi S. Resveratrol inhibits angiogenic response of cultured endothelial F-2 cells to vascular endothelial growth factor, but not to basic fibroblast growth factor. Biol Pharm Bull 2010; 33 (7) 1095-1100
  • 92 Hu Y, Sun CY, Huang J, Hong L, Zhang L, Chu ZB. Antimyeloma effects of resveratrol through inhibition of angiogenesis. Chin Med J (Engl) 2007; 120 (19) 1672-1677
  • 93 Chávez E, Reyes-Gordillo K, Segovia J , et al. Resveratrol prevents fibrosis, NF-kappaB activation and TGF-beta increases induced by chronic CCl4 treatment in rats. J Appl Toxicol 2008; 28 (1) 35-43
  • 94 Kim KH, Back JH, Zhu Y , et al. Resveratrol targets transforming growth factor-β2 signaling to block UV-induced tumor progression. J Invest Dermatol 2011; 131 (1) 195-202
  • 95 Vanamala J, Reddivari L, Radhakrishnan S, Tarver C. Resveratrol suppresses IGF-1 induced human colon cancer cell proliferation and elevates apoptosis via suppression of IGF-1R/Wnt and activation of p53 signaling pathways. BMC Cancer 2010; 10: 238-251
  • 96 Zou J, Huang Y, Chen Q , et al. Suppression of mitogenesis and regulation of cell cycle traverse by resveratrol in cultured smooth muscle cells. Int J Oncol 1999; 15 (4) 647-651
  • 97 Haider UG, Sorescu D, Griendling KK, Vollmar AM, Dirsch VM. Resveratrol increases serine15-phosphorylated but transcriptionally impaired p53 and induces a reversible DNA replication block in serum-activated vascular smooth muscle cells. Mol Pharmacol 2003; 63 (4) 925-932
  • 98 Mizutani K, Ikeda K, Yamori Y. Resveratrol inhibits AGEs-induced proliferation and collagen synthesis activity in vascular smooth muscle cells from stroke-prone spontaneously hypertensive rats. Biochem Biophys Res Commun 2000; 274 (1) 61-67
  • 99 Bertelli AA, Giovannini L, Giannessi D , et al. Antiplatelet activity of synthetic and natural resveratrol in red wine. Int J Tissue React 1995; 17 (1) 1-3
  • 100 Pace-Asciak CR, Hahn S, Diamandis EP, Soleas G, Goldberg DM. The red wine phenolics trans-resveratrol and quercetin block human platelet aggregation and eicosanoid synthesis: implications for protection against coronary heart disease. Clin Chim Acta 1995; 235 (2) 207-219
  • 101 Kirk RI, Deitch JA, Wu JM, Lerea KM. Resveratrol decreases early signaling events in washed platelets but has little effect on platelet in whole blood. Blood Cells Mol Dis 2000; 26 (2) 144-150
  • 102 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 (1) 77-79
  • 103 Newby AC, Zaltsman AB. Molecular mechanisms in intimal hyperplasia. J Pathol 2000; 190 (3) 300-309
  • 104 Ross R. Atherosclerosis—an inflammatory disease. N Engl J Med 1999; 340 (2) 115-126
  • 105 Galis ZS, Johnson C, Godin D , et al. Targeted disruption of the matrix metalloproteinase-9 gene impairs smooth muscle cell migration and geometrical arterial remodeling. Circ Res 2002; 91 (9) 852-859
  • 106 Cho A, Reidy MA. Matrix metalloproteinase-9 is necessary for the regulation of smooth muscle cell replication and migration after arterial injury. Circ Res 2002; 91 (9) 845-851
  • 107 Lee SJ, Kim MM. Resveratrol with antioxidant activity inhibits matrix metalloproteinase via modulation of SIRT1 in human fibrosarcoma cells. Life Sci 2011; 88 (11-12) 465-472
  • 108 Lee B, Moon SK. Resveratrol inhibits TNF-alpha-induced proliferation and matrix metalloproteinase expression in human vascular smooth muscle cells. J Nutr 2005; 135 (12) 2767-2773
  • 109 Miura D, Miura Y, Yagasaki K. Hypolipidemic action of dietary resveratrol, a phytoalexin in grapes and red wine, in hepatoma-bearing rats. Life Sci 2003; 73 (11) 1393-1400
  • 110 Zhu L, Luo X, Jin Z. Effect of resveratrol on serum and liver lipid profile and antioxidant activity in hyperlipidemia rats. Asian Aust J Anim Sci 2008; 21: 890-895
  • 111 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 (1) 190-194
  • 112 Do GM, Kwon EY, Kim HJ , et al. Long-term effects of resveratrol supplementation on suppression of atherogenic lesion formation and cholesterol synthesis in apo E-deficient mice. Biochem Biophys Res Commun 2008; 374 (1) 55-59
  • 113 Penumathsa SV, Thirunavukkarasu M, Koneru S , et al. Statin and resveratrol in combination induces cardioprotection against myocardial infarction in hypercholesterolemic rat. J Mol Cell Cardiol 2007; 42 (3) 508-516
  • 114 Nihei T, Miura Y, Yagasaki K. Inhibitory effect of resveratrol on proteinuria, hypoalbuminemia and hyperlipidemia in nephritic rats. Life Sci 2001; 68 (25) 2845-2852
  • 115 Ahn J, Cho I, Kim S, Kwon D, Ha T. Dietary resveratrol alters lipid metabolism-related gene expression of mice on an atherogenic diet. J Hepatol 2008; 49 (6) 1019-1028
  • 116 Rivera L, Morón R, Zarzuelo A, Galisteo M. Long-term resveratrol administration reduces metabolic disturbances and lowers blood pressure in obese Zucker rats. Biochem Pharmacol 2009; 77 (6) 1053-1063
  • 117 Turrens JF, Lariccia J, Nair MG. Resveratrol has no effect on lipoprotein profile and does not prevent peroxidation of serum lipids in normal rats. Free Radic Res 1997; 27 (6) 557-562
  • 118 De Castro M, Veiga APM, Pacheco MR. Plasma lipid profile of experimentally induced hyperlipidemic New Zealand white rabbits is not affected by resveratrol. J Appl Res 2009; 9: 18-22
  • 119 Hurlimann J, Thorbecke GJ, Hochwald GM. The liver as the site of C-reactive protein formation. J Exp Med 1966; 123 (2) 365-378
  • 120 Mackiewicz A, Speroff T, Ganapathi MK, Kushner I. Effects of cytokine combinations on acute phase protein production in two human hepatoma cell lines. J Immunol 1991; 146 (9) 3032-3037
  • 121 Pasceri V, Cheng JS, Willerson JT, Yeh ET. Modulation of C-reactive protein-mediated monocyte chemoattractant protein-1 induction in human endothelial cells by anti-atherosclerosis drugs. Circulation 2001; 103: 2531-2534
  • 122 Pasceri V, Willerson JT, Yeh ET. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation 2000; 102 (18) 2165-2168
  • 123 Torzewski M, Rist C, Mortensen RF , et al. C-reactive protein in the arterial intima: role of C-reactive protein receptor-dependent monocyte recruitment in atherogenesis. Arterioscler Thromb Vasc Biol 2000; 20 (9) 2094-2099
  • 124 Venugopal SK, Devaraj S, Jialal I. Effect of C-reactive protein on vascular cells: evidence for a proinflammatory, proatherogenic role. Curr Opin Nephrol Hypertens 2005; 14 (1) 33-37
  • 125 Verma S, Szmitko PE, Ridker PM. C-reactive protein comes of age. Nat Clin Pract Cardiovasc Med 2005; 2 (1) 29-36 , quiz 58
  • 126 Berk BC, Weintraub WS, Alexander RW. Elevation of C-reactive protein in “active” coronary artery disease. Am J Cardiol 1990; 65 (3) 168-172
  • 127 Rebuzzi AG, Quaranta G, Liuzzo G , et al. Incremental prognostic value of serum levels of troponin T and C-reactive protein on admission in patients with unstable angina pectoris. Am J Cardiol 1998; 82 (6) 715-719
  • 128 Buffon A, Liuzzo G, Biasucci LM , et al. Preprocedural serum levels of C-reactive protein predict early complications and late restenosis after coronary angioplasty. J Am Coll Cardiol 1999; 34 (5) 1512-1521
  • 129 de Winter RJ, Koch KT, van Straalen JP , et al. C-reactive protein and coronary events following percutaneous coronary angioplasty. Am J Med 2003; 115 (2) 85-90
  • 130 Kaur G, Rao LVM, Agrawal A, Pendurthi UR. Effect of wine phenolics on cytokine-induced C-reactive protein expression. J Thromb Haemost 2007; 5 (6) 1309-1317
  • 131 Avellone G, Di Garbo V, Campisi D , et al. Effects of moderate Sicilian red wine consumption on inflammatory biomarkers of atherosclerosis. Eur J Clin Nutr 2006; 60 (1) 41-47
  • 132 Schmidt AM, Stern D. Atherosclerosis and diabetes: the RAGE connection. Curr Atheroscler Rep 2000; 2 (5) 430-436
  • 133 Sakaguchi T, Yan SF, Yan SD , et al. Central role of RAGE-dependent neointimal expansion in arterial restenosis. J Clin Invest 2003; 111 (7) 959-972
  • 134 McNair ED, Wells CR, Mabood Qureshi A , et al. Soluble receptors for advanced glycation end products (sRAGE) as a predictor of restenosis following percutaneous coronary intervention. Clin Cardiol 2010; 33 (11) 678-685
  • 135 Zhou Z, Wang K, Penn MS , et al. Receptor for AGE (RAGE) mediates neointimal formation in response to arterial injury. Circulation 2003; 107 (17) 2238-2243
  • 136 Prasad K. Soluble receptor for advanced glycation end products (sRAGE) and cardiovascular disease. Int J Angiol 2006; 15: 57-68
  • 137 Hofmann MA, Drury S, Fu C , et al. RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides. Cell 1999; 97 (7) 889-901
  • 138 Reznikov LL, Waksman J, Azam T , et al. Effect of advanced glycation end products on endotoxin-induced TNF-alpha, IL-1beta and IL-8 in human peripheral blood mononuclear cells. Clin Nephrol 2004; 61 (5) 324-336
  • 139 Yan SD, Schmidt AM, Anderson GM , et al. Enhanced cellular oxidant stress by the interaction of advanced glycation end products with their receptors/binding proteins. J Biol Chem 1994; 269 (13) 9889-9897
  • 140 Wautier MP, Chappey O, Corda S, Stern DM, Schmidt AM, Wautier JL. Activation of NADPH oxidase by AGE links oxidant stress to altered gene expression via RAGE. Am J Physiol Endocrinol Metab 2001; 280 (5) E685-E694
  • 141 Yonekura H, Yamamoto Y, Sakurai S , et al. Novel splice variants of the receptor for advanced glycation end-products expressed in human vascular endothelial cells and pericytes, and their putative roles in diabetes-induced vascular injury. Biochem J 2003; 370 (Pt 3) 1097-1109
  • 142 Geroldi D, Falcone C, Emanuele E. Soluble receptor for advanced glycation end products: from disease marker to potential therapeutic target. Curr Med Chem 2006; 13 (17) 1971-1978
  • 143 Jing YH, Chen KH, Yang SH, Kuo PC, Chen JK. Resveratrol ameliorates vasculopathy in STZ-induced diabetic rats: role of AGE-RAGE signalling. Diabetes Metab Res Rev 2010; 26 (3) 212-222
  • 144 Zhang Y, Luo Z, Ma L, Xu Q, Yang Q, Si L. Resveratrol prevents the impairment of advanced glycosylation end products (AGE) on macrophage lipid homeostasis by suppressing the receptor for AGE via peroxisome proliferator-activated receptor gamma activation. Int J Mol Med 2010; 25 (5) 729-734
  • 145 Liu FC, Hung LF, Wu WL , et al. Chondroprotective effects and mechanisms of resveratrol in advanced glycation end products-stimulated chondrocytes. Arthritis Res Ther 2010; 12 (5) R167
  • 146 Grønbaek M, Becker U, Johansen D , et al. Type of alcohol consumed and mortality from all causes, coronary heart disease, and cancer. Ann Intern Med 2000; 133 (6) 411-419
  • 147 Klatsky AL, Friedman GD, Armstrong MA, Kipp H. Wine, liquor, beer, and mortality. Am J Epidemiol 2003; 158 (6) 585-595
  • 148 Renaud SC, Guéguen R, Siest G, Salamon R. Wine, beer, and mortality in middle-aged men from eastern France. Arch Intern Med 1999; 159 (16) 1865-1870
  • 149 Hayek T, Fuhrman B, Vaya J , et al. Reduced progression of atherosclerosis in apolipoprotein E-deficient mice following consumption of red wine, or its polyphenols quercetin or catechin, is associated with reduced susceptibility of LDL to oxidation and aggregation. Arterioscler Thromb Vasc Biol 1997; 17 (11) 2744-2752
  • 150 Stocker R, O'Halloran RA. Dealcoholized red wine decreases atherosclerosis in apolipoprotein E gene-deficient mice independently of inhibition of lipid peroxidation in the artery wall. Am J Clin Nutr 2004; 79 (1) 123-130
  • 151 Klurfeld DM, Kritchevsky DM. Differential effects of alcoholic beverages on experimental atherosclerosis in rabbits. Exp Mol Pathol 1981; 34 (1) 62-71
  • 152 da Luz PL, Serrano Júnior CV, Chacra AP , et al. The effect of red wine on experimental atherosclerosis: lipid-independent protection. Exp Mol Pathol 1999; 65 (3) 150-159
  • 153 Abbey M, Kerry NL. Flavonoids and their effects on LDL oxidation. Proc Nutr Soc Aust 1997; 21: 91-97
  • 154 Wang Z, Zou J, Cao K, Hsieh TC, Huang Y, Wu JM. Dealcoholized red wine containing known amounts of resveratrol suppresses atherosclerosis in hypercholesterolemic rabbits without affecting plasma lipid levels. Int J Mol Med 2005; 16 (4) 533-540
  • 155 Vinson JA, Teufel K, Wu N. Red wine, dealcoholized red wine, and especially grape juice, inhibit atherosclerosis in a hamster model. Atherosclerosis 2001; 156 (1) 67-72
  • 156 Do GM, Kwon EY, Kim HJ , et al. Long-term effects of resveratrol supplementation on suppression of atherogenic lesion formation and cholesterol synthesis in apo E-deficient mice. Biochem Biophys Res Commun 2008; 374 (1) 55-59
  • 157 Fukao H, Ijiri Y, Miura M , et al. Effect of trans-resveratrol on the thrombogenicity and atherogenicity in apolipoprotein E-deficient and low-density lipoprotein receptor-deficient mice. Blood Coagul Fibrinolysis 2004; 15 (6) 441-446
  • 158 Castro M, Pacheco MMR, Machado MRF. Morphology of aortic arch in rabbits with atherosclerosis treated with resveratrol. Int J Appl Res Vet Med 2009; 7: 190-195
  • 159 Wilson T, Knight TJ, Beitz DC, Lewis DS, Engen RL. Resveratrol promotes atherosclerosis in hypercholesterolemic rabbits. Life Sci 1996; 59: 15-21
  • 160 Hai O, Anwar K, Wirkowski PA, Voloshyna I, Carsons S, Reiss AB. Resveratrol exhibits anti-atherogenic properties by facilitating cholesterol efflux from THP-1 human monocytes/macrophages. Presented at Eastern Regional Meeting on American Federal for Medical Research, Washington, DC, April 6, 2010. Available at: www.afmr.org/abstracts/2010Eastern-Program.cgi