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Published in:

01-05-2012

Resveratrol in cardiovascular disease: what is known from current research?

Authors: Hong Wang, Yue-Jin Yang, Hai-Yan Qian, Qian Zhang, Hui Xu, Jian-Jun Li

Published in: Heart Failure Reviews | Issue 3/2012

Abstract

Resveratrol is a well-known antioxidant that exists in grape skin/seed, red wine, and the root of Polygonum cuspidatum, a traditional Chinese and Japanese medicinal material. Studies have found that resveratrol has many interesting properties, including anti-carcinogenic properties, anti-microbial and antiviral effects, the ability to reverse dyslipidemia and obesity, the ability to attenuate hyperglycemia and hyperinsulinemia, and the ability to protect endothelial function. Heart failure is the final consequence of the majority of cardiovascular diseases, and resveratrol has been shown to directly attenuate heart contraction. The cardiovascular protective capacities of resveratrol are associated with multiple molecular targets and may lead to the development of novel therapeutic strategies for atherosclerosis, ischemia/reperfusion, metabolic syndrome, and heart failure. This article will mainly review recently published basic researches about the protective cardiovascular effects of resveratrol because these results may lead to the development of new clinical therapeutics in patients.

Griendling KK, FitzGerald GA (2003) Oxidative stress and cardiovascular injury: part I: basic mechanisms and in vivo monitoring of ROS. Circulation 108:1912–1916PubMed

Griendling KK, FitzGerald GA (2003) Oxidative stress and cardiovascular injury: part II: animal and human studies. Circulation 108:2034–2040PubMed

Kawai J, Ando K, Tojo A, Shimosawa T, Takahashi K, Onozato ML, Yamasaki M, Ogita T, Nakaoka T, Fujita T (2004) Endogenous adrenomedullin protects against vascular response to injury in mice. Circulation 109:1147–1153PubMed

Matsui H, Shimosawa T, Itakura K, Xing G, Ando K, Fujita T (2004) Adrenomedullin can protect against pulmonary vascular remodeling induced by hypoxia. Circulation 109:2246–2251PubMed

Wang Q, Tompkins KD, Simonyi A, Korthuis RJ, Sun AY, Sun GY (2006) Apocynin protects against global cerebral ischemia-reperfusion-induced oxidative stress and injury in the gerbil hippocampus. Brain Res 1090:182–189PubMed

Wang H, Shimosawa T, Matsui H, Kaneko T, Ogura S, Uetake Y, Takenaka K, Yatomi Y, Fujita T (2008) Paradoxical mineralocorticoid receptor activation and left ventricular diastolic dysfunction under high oxidative stress conditions. J Hypertens 26:1453–1462PubMed

Matsui H, Ando K, Kawarazaki H, Nagae A, Fujita M, Shimosawa T, Nagase M, Fujita T (2008) Salt excess causes left ventricular diastolic dysfunction in rats with metabolic disorder. Hypertension 52:287–294PubMed

Nagae A, Fujita M, Kawarazaki H, Matsui H, Ando K, Fujita T (2009) Sympathoexcitation by oxidative stress in the brain mediates arterial pressure elevation in obesity-induced hypertension. Circulation 119:978–986PubMed

Houston MC (2010) The role of cellular micronutrient analysis, nutraceuticals, vitamins, antioxidants and minerals in the prevention and treatment of hypertension and cardiovascular disease. Ther Adv Cardiovasc Dis 4:165–183PubMed

10.

Yusuf S, Dagenais G, Pogue J, Bosch J, Sleight P (2000) Vitamin E supplementation and cardiovascular events in high-risk patients. The heart outcomes prevention evaluation study investigators. N Engl J Med 342:154–160PubMed

11.

Marchioli R, Levantesi G, Macchia A, Marfisi RM, Nicolosi GL, Tavazzi L, Tognoni G, Valagussa F, GISSI-Prevenzione Investigators (2006) Vitamin E increases the risk of developing heart failure after myocardial infarction: results from the GISSI-prevenzione trial. J Cardiovasc Med (Hagerstown) 7:347–350

12.

Miller ER III, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E (2005) Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 142:37–46PubMed

13.

Bertrand ME (2004) Provision of cardiovascular protection by ACE inhibitors: a review of recent trials. Curr Med Res Opin 20:1559–1569PubMed

14.

Ono H, Minatoguchi S, Watanabe K, Yamada Y, Mizukusa T, Kawasaki H, Takahashi H, Uno T, Tsukamoto T, Hiei K, Fujiwara H (2008) Candesartan decreases carotid intima-media thickness by enhancing nitric oxide and decreasing oxidative stress in patients with hypertension. Hypertens Res 31:271–279PubMed

15.

Ishimitsu T, Numabe A, Masuda T, Akabane T, Okamura A, Minami J, Matsuoka H (2009) Angiotensin-II receptor antagonist combined with calcium channel blocker or diuretic for essential hypertension. Hypertens Res 32:962–968PubMed

16.

Sasaki H, Saiki A, Endo K, Ban N, Yamaguchi T, Kawana H, Nagayama D, Ohhira M, Oyama T, Miyashita Y, Shirai K (2009) Protective effects of efonidipine, a T- and L-type calcium channel blocker, on renal function and arterial stiffness in type 2 diabetic patients with hypertension and nephropathy. J Atheroscler Thromb 16:568–575PubMed

17.

Li J, Sun YM, Wang LF, Li ZQ, Pan W, Cao HY (2010) Comparison of effects of simvastatin versus atorvastatin on oxidative stress in patients with coronary heart disease. Clin Cardiol 33:222–227PubMed

18.

Papanas N, Maltezos E (2009) Oral antidiabetic agents: anti-atherosclerotic properties beyond glucose lowering? Curr Pharm Des 15:3179–3192PubMed

19.

Hopkins AL (2008) Network pharmacology: the next paradigm in drug discovery. Nat Chem Biol 4:682–690PubMed

20.

Baur JA, Sinclair DA (2006) Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov 5:493–506PubMed

21.

Opie LH, Lecour S (2007) The red wine hypothesis: from concepts to protective signalling molecules. Eur Heart J 28:1683–1693PubMed

22.

Karlsson J, Emgard M, Brundin P, Burkitt MJ (2000) Trans-resveratrol protects embryonic mesencephalic cells from tert-Butyl hydroperoxide: electron paramagnetic resonance spin trapping evidence for a radical scavenging mechanism. J Neurochem 75:141–150PubMed

23.

Spanier G, Xu H, Xia N, Tobias S, Deng S, Wojnowski L, Forstermann U, Li H (2009) Resveratrol reduces endothelial oxidative stress by modulating the gene expression of superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPx1) and NADPH oxidase subunit (Nox4). J Physiol Pharmacol 60(Suppl 4):111–116PubMed

24.

Yildiz F, Terzi A, Coban S, Celik H, Aksoy N, Bitiren M, Cakir H, Ozdogan MK (2009) Protective effects of resveratrol on small intestines against intestinal ischemia-reperfusion injury in rats. J Gastroenterol Hepatol 24:1781–1785PubMed

25.

Dolinsky VW, Chan AY, Robillard Frayne I, Light PE, Des Rosiers C, Dyck JR (2009) Resveratrol prevents the prohypertrophic effects of oxidative stress on LKB1. Circulation 119:1643–1652PubMed

26.

Thirunavukkarasu M, Penumathsa SV, Koneru S, Juhasz B, Zhan L, Otani H, Bagchi D, Das DK, Maulik N (2007) Resveratrol alleviates cardiac dysfunction in streptozotocin-induced diabetes: role of nitric oxide, thioredoxin and heme oxygenase. Free Radic Biol Med 43:720–729PubMed

27.

Tanno M, Kuno A, Yano T, Miura T, Hisahara S, Ishikawa S, Shimamoto K, Horio Y (2010) Induction of manganese superoxide dismutase by nuclear translocation and activation of SIRT1 promotes cell survival in chronic heart failure. J Biol Chem 285:8375–8382PubMed

28.

Ungvari Z, Orosz Z, Rivera A, Labinskyy N, Xiangmin Z, Olson S, Podlutsky A, Csiszar A (2007) Resveratrol increases vascular oxidative stress resistance. Am J Physiol Heart Circ Physiol 292:H2417–H2424PubMed

29.

Ferretti G, Bacchetti T, Menanno F, Curatola G (2004) Effect of genistein against copper-induced lipid peroxidation of human high density lipoproteins (HDL). Atherosclerosis 172:55–61PubMed

30.

Belguendouz L, Fremont L, Linard A (1997) Resveratrol inhibits metal ion-dependent and independent peroxidation of porcine low-density lipoproteins. Biochem Pharmacol 53:1347–1355PubMed

31.

Wallerath T, Deckert G, Ternes T, Anderson H, Li H, Witte K, Förstermann U (2002) Resveratrol, a polyphenolic phytoalexin present in red wine, enhances expression and activity of endothelial nitric oxide synthase. Circulation 106:1652–1658PubMed

32.

Zou JG, Wang ZR, Huang YZ, Cao KJ, Wu JM (2003) Effect of red wine polyphenol resveratrol on endothelial function in hypercholesterolemic rabbits. Int J Mol Med 11:317–320PubMed

33.

Csiszar A, Labinskyy N, Olson S, Pinto JT, Gupte S, Wu JM, Hu F, Ballabh P, Podlutsky A, Losonczy G, de Cabo R, Mathew R, Wolin MS, Ungvari Z (2009) Resveratrol prevents monocrotaline-induced pulmonary hypertension in rats. Hypertension 54:668–675PubMed

34.

Arunachalam G, Yao H, Sundar IK, Caito S, Rahman I (2010) SIRT1 regulates oxidant- and cigarette smoke-induced eNOS acetylation in endothelial cells: role of resveratrol. Biochem Biophys Res Commun 393:66–72PubMed

35.

Hattori R, Otani H, Maulik N, Das DK (2002) Pharmacological preconditioning with resveratrol: role of nitric oxide. Am J Physiol Heart Circ Physiol 282:H1988–H1995PubMed

36.

Lin KY, Lin SC (2004) A tale of two molecules: nitric oxide and asymmetric dimethylarginine. Acta Cardiol Sin 20:201–211

37.

DeMarco VG, Johnson MS, Whaley-Connell AT, Sowers JR (2010) Cytokine abnormalities in the etiology of the cardiometabolic syndrome. Curr Hypertens Rep 12:93–98PubMed

38.

Rizvi AA (2010) Hypertension, obesity, and inflammation: the complex designs of a deadly trio. Metab Syndr Relat Disord 8:287–294PubMed

39.

Frémont L (2000) Biological effects of resveratrol. Life Sci 66:663–673PubMed

40.

Sharma S, Chopra K, Kulkarni SK, Agrewala JN (2007) Resveratrol and curcumin suppress immune response through CD28/CTLA-4 and CD80 co-stimulatory pathway. Clin Exp Immunol 147:155–163PubMed

41.

Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, Fong HH, Farnsworth NR, Kinghorn AD, Mehta RG, Moon RC, Pezzuto JM (1997) Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 275:218–220PubMed

42.

Szewczuk LM, Penning TM (2004) Mechanism-based inactivation of COX-1 by red wine m-hydroquinones: a structure-activity relationship study. J Nat Prod 67:1777–1782PubMed

43.

Martinez J, Moreno JJ (2000) Effect of resveratrol, a natural polyphenoliccompound, on reactive oxygen species and prostaglandin production. Biochem Pharmacol 59:865–870PubMed

44.

Subbaramaiah K, Chung WJ, Michaluart P, Telang N, Tanabe T, Inoue H, Jang M, Pezzuto JM, Dannenberg AJ (1998) Resveratrol inhibits cyclooxygenase-2 transcription and activity in phorbol ester-treated human mammary epithelial cells. J Biol Chem 273:21875–21882PubMed

45.

Dave M, Attur M, Palmer G, Al-Mussawir HE, Kennish L, Patel J, Abramson SB (2008) The antioxidant resveratrol protects against chondrocyte apoptosis via effects on mitochondrial polarization and ATP production. Arthritis Rheum 58:2786–2797PubMed

46.

Kang SS, Cuendet M, Endringer DC, Croy VL, Pezzuto JM, Lipton MA (2009) Synthesis and biological evaluation of a library of resveratrol analogues as inhibitors of COX-1, COX-2 and NF-kB. Bioorg Med Chem 17:1044–1054PubMed

47.

Leiro J, Arranz JA, Fraiz N, Sanmartin ML, Quezada E, Orallo F (2005) Effect of cis-resveratrol on genes involved in nuclear factor kappa B signaling. Int Immunopharmacol 5:393–406PubMed

48.

Karlsen A, Paur I, Bøhn SK, Sakhi AK, Borge GI, Serafini M, Erlund I, Laake P, Tonstad S, Blomhoff R (2010) Bilberry juice modulates plasma concentration of NF-kappaB related inflammatory markers in subjects at increased risk of CVD. Eur J Nutr 49:345–355PubMed

49.

Shen MY, Hsiao G, Liu CL, Fong TH, Lin KH, Chou DS, Sheu JR (2007) Inhibitory mechanisms of resveratrol in platelet activation: pivotal roles of p38 MAPK and NO/cyclic GMP. Br J Haematol 139(3):475–485PubMed

50.

Yang YM, Chen JZ, Wang XX, Wang SJ, Hu H, Wang HQ (2008) Resveratrol attenuates thromboxane A2 receptor agonist-induced platelet activation by reducing phospholipase C activity. Eur J Pharmacol 583:148–155PubMed

51.

Lin KH, Hsiao G, Shih CM, Chou DS, Sheu JR (2009) Mechanisms of resveratrol-induced platelet apoptosis. Cardiovasc Res 83:575–585PubMed

52.

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 (2006) Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 127:1109–1122PubMed

53.

Sancho J, Villarreal G Jr, Zhang Y, García-Cardeña G (2010) Activation of SIRT1 by resveratrol induces KLF2 expression conferring an endothelial vasoprotective phenotype. Cardiovasc Res 85:514–519

54.

Villarreal G Jr, Zhang Y, Larman HB, Gracia-Sancho J, Koo A, García-Cardeña G (2010) Defining the regulation of KLF4 expression and its downstream transcriptional targets in vascular endothelial cells. Biochem Biophys Res Commun 391:984–989PubMed

55.

Ungvari ZI, Bagi Z, Feher A, Recchia FA, Sonntag WE, Pearson KJ, de Cabo R, Csiszar A (2010) Resveratrol confers endothelial protection via activation of the antioxidant transcription factor Nrf2. Am J Physiol Heart Circ Physiol 299:H18–H24PubMed

56.

Robich MP, Osipov RM, Nezafat R, Feng J, Clements RT, Bianchi C, Boodhwani M, Coady MA, Laham RJ, Sellke FW (2010) Resveratrol improves myocardial perfusion in a swine model of hypercholesterolemia and chronic myocardial ischemia. Circulation 122(11 Suppl):S142–S149PubMed

57.

Le Brocq M, Leslie SJ, Milliken P, Megson IL (2008) Endothelial dysfunction: from molecular mechanisms to measurement, clinical implications, and therapeutic opportunities. Antioxid Redox Signal 10:1631–1674PubMed

58.

Das DK, Mukherjee S, Ray D (2010) Resveratrol and red wine, healthy heart and longevity. Heart Fail Rev 15:467–477PubMed

59.

Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch 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 (2006) Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444:337–342PubMed

60.

Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR, Frye RA, Mayo MW (2004) Modulation of NF-κB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J 23:2369–2380PubMed

61.

Vaziri H, Dessain SK, Ng Eaton E, Imai SI, Frye RA, Pandita TK, Guarente L, Weinberg RA (2001) hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. Cell 107:149–159PubMed

62.

Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P (2005) Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature 434:113–118PubMed

63.

Subramaniam D, Ramalingam S, Houchen CW, Anant S (2010) Cancer stem cells: a novel paradigm for cancer prevention and treatment. Mini Rev Med Chem 10:359–371PubMed

64.

Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, Puigserver P, Carlsson E, Ridderstråle M, Laurila E, Houstis N, Daly MJ, Patterson N, Mesirov JP, Golub TR, Tamayo P, Spiegelman B, Lander ES, Hirschhorn JN, Altshuler D (2003) Groop LC (2003) PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet 34:267–273PubMed

65.

Picard F, Kurtev M, Chung N, Topark-Ngarm A, Senawong T, Machado De Oliveira R, Leid M, McBurney MW, Guarente L (2004) Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-γ. Nature 429:771–776PubMed

66.

Bai L, Pang WJ, Yang YJ, Yang GS (2008) Modulation of Sirt1 by resveratrol and nicotinamide alters proliferation and differentiation of pig preadipocytes. Mol Cell Biochem 307:129–140PubMed

67.

Mader I, Wabitsch M, Debatin KM, Fischer-Posovszky P, Fulda S (2010) Identification of a novel proapoptotic function of resveratrol in fat cells: SIRT1-independent sensitization to TRAIL-induced apoptosis. FASEB J 24:1997–2009PubMed

68.

Miura D, Miura Y (2003) Yagasaki K (2003) Hypolipidemic action of dietary resveratrol, a phytoalexin in grapes and red wine, in hepatomabearing rats. Life Sci 73:1393–1400PubMed

69.

Fremont L, Belguendouz L, Delpal S (1999) Antioxidant activity of resveratrol and alcohol-free wine polyphenols related to LDL oxidation and polyunsaturated fatty acids. Life Sci 64:2511–2521PubMed

70.

Araim O, Ballantyne J, Waterhouse AL, Sumpio BE (2002) Inhibition of vascular smooth muscle cell proliferation with red wine and red wine polyphenols. J Vasc Surg 35:1226–1232PubMed

71.

Cho IJ, Ahn JY, Kim S, Choi MS, Ha TY (2008) Resveratrol attenuates the expression of HMG-CoA reductase mRNA in hamsters. Biochem Biophys Res Commun 367:190–194PubMed

72.

Weber O, Bischoff H, Schmeck C, Böttcher MF (2010) Cholesteryl ester transfer protein and its inhibition. Cell Mol Life Sci 67:3139–3149PubMed

73.

Berrougui H, Grenier G, Loued S, Drouin G, Khalil A (2009) A new insight into resveratrol as an atheroprotective compound: inhibition of lipid peroxidation and enhancement of cholesterol efflux. Atherosclerosis 207:420–427PubMed

74.

Do GM, Kwon EY, Kim HJ, Jeon SM, Ha TY, Park T, Choi MS (2008) Long-term effects of resveratrol supplementation on suppression of atherogenic lesion formation and cholesterol synthesis in apo E-deficient mice. Biochem Biophys Res Commun 374:55–59PubMed

75.

Iannelli P, Zarrilli V, Varricchio E, Tramontano D, Mancini FP (2007) The dietary antioxidant resveratrol affects redox changes of PPARα activity. Nutr Metab Cardiovasc Dis 17:247–256PubMed

76.

Zhang Y, Luo Z, Ma L, Xu Q, Yang Q, Si L (2010) 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 25:729–734PubMed

77.

Schimmack G, Defronzo RA, Musi N (2006) AMP-activated protein kinase: role in metabolism and therapeutic implications. Diabetes Obes Metab 8:591–602PubMed

78.

Fullerton MD, Steinberg GR (2010) SIRT1 takes a backseat to AMPK in the regulation of insulin sensitivity by resveratrol. Diabetes 59:551–553PubMed

79.

Iwabu M, Yamauchi T, Okada-Iwabu M, Sato K, Nakagawa T, Funata M, Yamaguchi M, Namiki S, Nakayama R, Tabata M, Ogata H, Kubota N, Takamoto I, Hayashi YK, Yamauchi N, Waki H, Fukayama M, Nishino I, Tokuyama K, Ueki K, Oike Y, Ishii S, Hirose K, Shimizu T, Touhara K, Kadowaki T (2010) Adiponectin and AdipoR1 regulate PGC-1a and mitochondria by Ca²⁺ and AMPK/SIRT1. Nature 464:1313–1319PubMed

80.

Ja¨ger S, Handschin C, St-Pierre J, Spiegelman BM (2007) AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1a. Proc Natl Acad Sci USA 104:12017–12022

81.

Patti ME, Butte AJ, Crunkhorn S, Cusi K, Berria R, Kashyap S, Miyazaki Y, Kohane I, Costello M, Saccone R, Landaker EJ, Goldfine AB, Mun E, DeFronzo R, Finlayson J, Kahn CR, Mandarino LJ (2003) Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: potential role of PGC1 and NRF1. Proc Natl Acad Sci USA 100:8466–8471PubMed

82.

Deng JY, Hsieh PS, Huang JP, Lu LS, Hung LM (2008) Activation of estrogen receptor is crucial for resveratrol-stimulating muscular glucose uptake via both insulin-dependent and -independent pathways. Diabetes 57:1814–1823PubMed

83.

Ribas V, Nguyen MT, Henstridge DC, Nguyen AK, Beaven SW, Watt MJ, Hevener AL (2010) Impaired oxidative metabolism and inflammation are associated with insulin resistance in ER{alpha} deficient mice. Am J Physiol Endocrinol Metab 298:E304–E319PubMed

84.

Barros RP, Gabbi C, Morani A, Warner M, Gustafsson JA (2009) Participation of ERalpha and ERbeta in glucose homeostasis in skeletal muscle and white adipose tissue. Am J Physiol Endocrinol Metab 297:E124–E133PubMed

85.

Lundholm L, Bryzgalova G, Gao H, Portwood N, Fält S, Berndt KD, Dicker A, Galuska D, Zierath JR, Gustafsson JA, Efendic S, Dahlman-Wright K, Khan A (2008) The estrogen receptor {alpha}-selective agonist propyl pyrazole triol improves glucose tolerance in ob/ob mice; potential molecular mechanisms. J Endocrinol 199:275–286PubMed

86.

Barros RP, Machado UF, Gustafsson JA (2006) Estrogen receptors: new players in diabetes mellitus. Trends Mol Med 12:425–431PubMed

87.

Cho DI, Koo NY, Chung WJ, Kim TS, Ryu SY, Im SY, Kim KM (2002) Effects of resveratrol-related hydroxystilbenes on the nitric oxide production in macrophage cells: structural requirements and mechanism of action. Life Sci 71:2071–2082PubMed

88.

Klinge CM, Wickramasinghe NS, Ivanova MM, Dougherty SM (2008) Resveratrol stimulates nitric oxide production by increasing estrogen receptor α-Src-caveolin-1 interaction and phosphorylation in human umbilical vein endothelial cells. FASEB J 22:2185–2197PubMed

89.

Urbich C, Dimmeler S (2005) Risk factors for coronary artery disease, circulating endothelial progenitor cells, and the role of HMG-CoA reductase inhibitors. Kidney Int 67:1672–1676PubMed

90.

Lefèvre J, Michaud SE, Haddad P, Dussault S, Ménard C, Groleau J, Turgeon J, Rivard A (2007) Moderate consumption of red wine (cabernet sauvignon) improves ischemia-induced neovascularization in ApoE-deficient mice: effect on endothelial progenitor cells and nitric oxide. FASEB J 21:3845–3852PubMed

91.

Gan L, Matsuura H, Ichiki T, Yin X, Miyazaki R, Hashimoto T, Cui J, Takeda K, Sunagawa K (2009) Improvement of neovascularization capacity of bone marrow mononuclear cells from diabetic mice by ex vivo pretreatment with resveratrol. Hypertens Res 32:542–547PubMed

92.

Xia L, Wang XX, Hu XS, Guo XG, Shang YP, Chen HJ, Zeng CL, Zhang FR, Chen JZ (2008) Resveratrol reduces endothelial progenitor cells senescence through augmentation of telomerase activity by Akt-dependent mechanisms. Br J Pharmacol 155:387–394PubMed

93.

Huang PH, Chen YH, Tsai HY, Chen JS, Wu TC, Lin FY, Sata M, Chen JW, Lin SJ (2010) Intake of red wine increases the number and functional capacity of circulating endothelial progenitor cells by enhancing nitric oxide bioavailability. Arterioscler Thromb Vasc Biol 30:869–877PubMed

94.

Balestrieri ML, Schiano C, Felice F, Casamassimi A, Balestrieri A, Milone L, Servillo L, Napoli C (2008) Effect of low doses of red wine and pure resveratrol on circulating endothelial progenitor cells. J Biochem 143:179–186PubMed

95.

Wang XB, Huang J, Zou JG, Su EB, Shan QJ, Yang ZJ, Cao KJ (2007) Effects of resveratrol on number and activity of endothelial progenitor cells from human peripheral blood. Clin Exp Pharmacol Physiol 34:1109–1115PubMed

96.

Dhawan SS, Avati Nanjundappa RP, Branch JR, Taylor WR, Quyyumi AA, Jo H, McDaniel MC, Suo J, Giddens D, Samady H (2010) Shear stress and plaque development. Expert Rev Cardiovasc Ther 8:545–556PubMed

97.

Dai G, Vaughn S, Zhang Y, Wang ET, Garcia-Cardena G, Gimbrone MA Jr (2007) Biomechanical forces in atherosclerosis-resistant vascular regions regulate endothelial redox balance via phosphoinositol 3-kinase/Akt-dependent activation of Nrf2. Circ Res 101:723–733PubMed

98.

Hosoya T, Maruyama A, Kang MI, Kawatani Y, Shibata T, Uchida K, Warabi E, Noguchi N, Itoh K, Yamamoto M (2005) Differential responses of the Nrf2-Keap1 system to laminar and oscillatory shear stresses in endothelial cells. J Biol Chem 280:27244–27250PubMed

99.

Imamura G, Bertelli AA, Bertelli A, Otani H, Maulik N, Das DK (2002) Pharmacological preconditioning with resveratrol: an insight with iNOS knockout mice. Am J Physiol Heart Circ Physiol 282:H1996–H2003PubMed

100.

Penumathsa SV, Maulik N (2009) Resveratrol: a promising agent in promoting cardioprotection against coronary heart disease. Can J Physiol Pharmacol 87:275–286PubMed

101.

Mokni M, Limam F, Elkahoui S, Amri M, Aouani E (2007) Strong cardioprotective effect of resveratrol, a red wine polyphenol, on isolated rat hearts after ischemia/reperfusion injury. Arch Biochem Biophys 457:1–6PubMed

102.

Raval AP, Lin HW, Dave KR, Defazio RA, Della Morte D, Kim EJ, Perez-Pinzon MA (2008) Resveratrol and ischemic preconditioning in the brain. Curr Med Chem 15:1545–1551PubMed

103.

Inoue H, Jiang XF, Katayama T, Osada S, Umesono K, Namura S (2003) Brain protection by resveratrol and fenofibrate against stroke requires peroxisome proliferator-activated receptor alpha in mice. Neurosci Lett 352:203–206PubMed

104.

Gurusamy N, Lekli I, Mukherjee S, Ray D, Ahsan MK, Gherghiceanu M, Popescu LM, Das DK (2010) Cardioprotection by resveratrol: a novel mechanism via autophagy involving the mTORC2 pathway. Cardiovasc Res 86:103–112PubMed

105.

Gurusamy N, Das DK (2009) Autophagy, redox signaling, and ventricular remodeling. Antioxid Redox Signal 11:1975–1988PubMed

106.

Behbahani J, Thandapilly SJ, Louis XL, Huang Y, Shao Z, Kopilas MA, Wojciechowski P, Netticadan T, Anderson HD (2010) Resveratrol and small artery compliance and remodeling in the spontaneously hypertensive rat. Am J Hypertens 23:1273–1278PubMed

107.

Thandapilly SJ, Wojciechowski P, Behbahani J, Louis XL, Yu L, Juric D, Kopilas MA, Anderson HD, Netticadan T (2010) Resveratrol prevents the development of pathological cardiac hypertrophy and contractile dysfunction in the SHR without lowering blood pressure. Am J Hypertens 23:192–196PubMed

108.

Juric D, Wojciechowski P, Das DK, Netticadan T (2007) Prevention of concentric hypertrophy and diastolic impairment in aortic-banded rats treated with resveratrol. Am J Physiol Heart Circ Physiol 292:H2138–H2143PubMed

109.

Chan AY, Soltys CL, Young ME, Proud CG, Dyck JR (2004) Activation of AMP-activated protein kinase inhibits protein synthesis associated with hypertrophy in the cardiac myocyte. J Biol Chem 279:32771–32779PubMed

110.

Noga AA, Soltys CL, Barr AJ, Kovacic S, Lopaschuk GD, Dyck JR (2007) Expression of an active LKB1 complex in cardiac myocytes results in decreased protein synthesis associated with phenylephrine-induced hypertrophy. Am J Physiol Heart Circ Physiol 292:H1460–H1469PubMed

111.

Chan AY, Dolinsky VW, Soltys CL, Viollet B, Baksh S, Light PE, Dyck JR (2008) Resveratrol inhibits cardiac hypertrophy via AMP-activated protein kinase and Akt. J Biol Chem 283:24194–24201PubMed

112.

Langley E, Pearson M, Faretta M, Bauer UM, Frye RA, Minucci S, Pelicci PG, Kouzarides T (2002) Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence. EMBO J 21:2383–2396PubMed

113.

Pillai JB, Isbatan A, Imai S, Gupta MP (2005) Poly(ADP-ribose) polymerase-1-dependent cardiac myocyte cell death during heart failure is mediated by NAD+ depletion and reduced Sir2alpha deacetylase activity. J Biol Chem 280:43121–43130PubMed

114.

Gaemperli O, Liga R, Spyrou N, Rosen SD, Foale R, Kooner JS, Rimoldi OE, Camici PG (2010) Myocardial beta-adrenoceptor down-regulation early after infarction is associated with long-term incidence of congestive heart failure. Eur Heart J 31:1722–1729PubMed

115.

Burstein B, Maguy A, Clement R, Gosselin H, Poulin F, Ethier N, Tardif JC, Hebert TE, Calderone A, Nattel S (2007) Effects of resveratrol (trans-3,5,4′-Trihydroxystilbene) treatment on cardiac remodeling following myocardial infarction. J Pharmacol Exp Ther 323:916–923PubMed

116.

Xin P, Pan Y, Zhu W, Huang S, Wei M, Chen C (2010) Favorable effects of resveratrol on sympathetic neural remodeling in rats following myocardial infarction. Eur J Pharmacol 649:293–300PubMed

117.

Schmidt AG, Zhai J, Carr AN, Gerst MJ, Lorenz JN, Pollesello P, Annila A, Hoit BD, Kranias EG (2002) Structural and functional implications of the phospholamban hinge domain: impaired SR Ca2+ uptake as a primary cause of heart failure. Cardiovasc Res 56:248–259PubMed

118.

Sulaiman M, Matta MJ, Sunderesan NR, Gupta MP, Periasamy M, Gupta M (2010) Resveratrol, an activator of SIRT1, upregulates sarcoplasmic calcium ATPase and improves cardiac function in diabetic cardiomyopathy. Am J Physiol Heart Circ Physiol 298:H833–H843PubMed

119.

Ding Y, Choi KJ, Kim JH, Han X, Piao Y, Jeong JH, Choe W, Kang I, Ha J, Forman HJ, Lee J, Yoon KS, Kim SS (2008) Endogenous hydrogen peroxide regulates glutathione redox via nuclear factor erythroid 2-related factor 2 downstream of phosphatidylinositol 3-kinase during muscle differentiation. Am J Pathol 172:1529–1541PubMed

120.

Yang YJ, Qian HY, Geng YJ, Gao RL, Dou KF, Yang GS, Li JJ, Shen R, He ZX, Lu MJ, Zhao SH (2008) Atorvastatin treatment improves survival and effects of implanted mesenchymal stem cells in post-infarct swine hearts. Eur Heart J 29:1578–1590PubMed

121.

Yang YJ, Qian HY, Huang J, Li JJ, Gao RL, Dou KF, Yang GS, Willerson JT, Geng YJ (2009) Simvastatin improves microenvironment and facilitates survival and activities of the bone marrow mesenchymal stem cells implanted in post-infarct swine hearts. Arterioscler Thromb Vasc Biol 29:2076–2082PubMed

122.

Gurusamy N, Ray D, Lekli I, Das DK (2010) Red wine antioxidant resveratrol-modified cardiac stem cells regenerate infarcted myocardium. J Cell Mol Med 14:2235–2239PubMed

123.

Gorbunov N, Petrovski G, Gurusamy N, Ray D, Kim DH, Das DK Regeneration of infarcted myocardium with resveratrol-modified cardiac stem cells. J Cell Mol Med. doi:10.1111/j.1582-4934.2011.01281.x

124.

Ekshyyan VP, Hebert VY, Khandelwal A, Dugas TR (2007) Resveratrol inhibits rat aortic vascular smooth muscle cell proliferation via estrogen receptor dependent nitric oxide production. J Cardiovasc Pharmacol 50:83–93PubMed

125.

Venkatesan B, Valente AJ, Reddy VS, Siwik DA, Chandrasekar B (2009) Resveratrol blocks interleukin-18-EMMPRIN cross-regulation and smooth muscle cell migration. Am J Physiol Heart Circ Physiol 297:H874–H886PubMed

126.

Wang Z, Chen Y, Labinskyy N, Hsieh TC, Ungvari Z, Wu JM (2006) Regulation of proliferation and gene expression in cultured human aortic smooth muscle cells by resveratrol and standardized grape extracts. Biochem Biophys Res Commun 346:367–376PubMed

127.

Zou J, Huang Y, Cao K, Yang G, Yin H, Len J, Hsieh TC, Wu JM (2000) Effect of resveratrol on intimal hyperplasia after endothelial denudation in an experimental rabbit model. Life Sci 68:153–163PubMed

128.

Rattan SI, Fernandes RA, Demirovic D, Dymek B, Lima CF (2009) Heat stress and hormetin-induced hormesis in human cells: effects on aging, wound healing, angiogenesis, and differentiation. Dose Response 7:90–103PubMed

129.

Juhasz B, Mukherjee S, Das DK (2010) Hormetic response of resveratrol against cardioprotection. Exp Clin Cardiol 15:e134–e138PubMed

130.

Cecchinato V, Chiaramonte R, Nizzardo M, Cristofaro B, Basile A, Sherbet GV, Comi P (2007) Resveratrol-induced apoptosis in human T-cell acute lymphoblastic leukaemia MOLT-4 cells. Biochem Pharmacol 74:1568–1574PubMed

131.

Majumdar AP, Banerjee S, Nautiyal J, Patel BB, Patel V, Du J, Yu Y, Elliott AA, Levi E, Sarkar FH (2009) Curcumin synergizes with resveratrol to inhibit colon cancer. Nutr Cancer 61:544–553PubMed

132.

Reagan-Shaw S, Nihal M, Ahmad N (2008) Dose translation from animal to human studies revisited. FASEB J 22:659–661PubMed

133.

Patel KR, Scott E, Brown VA, Gescher AJ, Steward WP, Brown K (2011) Clinical trials of resveratrol. Ann N Y Acad Sci 1215:161–169PubMed

134.

Ghanim H, Sia CL, Abuaysheh S, Korzeniewski K, Patnaik P, Marumganti A, Chaudhuri A, Dandona P (2010) An antiinflammatory and reactive oxygen species suppressive effects of an extract of Polygonum Cuspidatum containing resveratrol. J Clin Endocrinol Metab 95:E1–E8PubMed

135.

Boocock DJ, Faust GE, Patel KR, Schinas AM, Brown VA, Ducharme MP, Booth TD, Crowell JA, Perloff M, Gescher AJ, Steward WP, Brenner DE (2007) Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent. Cancer Epidemiol Biomarkers Prev 16:1246–1252PubMed

136.

Camins A, Sureda FX, Junyent F, Verdaguer E, Folch J, Beas-Zarate C, Pallas M (2010) An overview of investigational antiapoptotic drugs with potential application for the treatment of neurodegenerative disorders. Expert Opin Investig Drugs 19:587–604PubMed

137.

Almeida L, Vaz-da-Silva M, Falcão A, Soares E, Costa R, Loureiro AI, Fernandes-Lopes C, Rocha JF, Nunes T, Wright L, Soares-da-Silva P (2009) Pharmacokinetic and safety profile of trans-resveratrol in a rising multiple-dose study in healthy volunteers. Mol Nutr Food Res 53(Suppl 1):S7–S15PubMed

Title: Resveratrol in cardiovascular disease: what is known from current research?
Authors: Hong Wang
Yue-Jin Yang
Hai-Yan Qian
Qian Zhang
Hui Xu
Jian-Jun Li
Publication date: 01-05-2012
Publisher: Springer US
Published in: Heart Failure Reviews / Issue 3/2012
Print ISSN: 1382-4147
Electronic ISSN: 1573-7322
DOI: https://doi.org/10.1007/s10741-011-9260-4

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