The role of oxidative stress, antioxidants and vascular inflammation in cardiovascular disease (a review)

Touyz, 2005, Molecular and cellular mechanism in vascular injury in hypertension: role of angiotensin II, Curr Opin Nephrol Hypertens, 14, 125, 10.1097/00041552-200503000-00007 Griendling, 2003, Oxidative stress and cardiovascular injury part 1: basic mechanisms and in vivo monitoring of ROS, Circulation, 108, 1912, 10.1161/01.CIR.0000093660.86242.BB Mazor, 2010, Tumor necrosis factor-α: a possible priming agent for the polymorphonuclear leukocyte-reduced nicotinamide-adenine dinucleotide phosphate oxidase in hypertension, Hypertension, 55, 353, 10.1161/HYPERTENSIONAHA.109.144154 Fukutomi, 2013, Low-grade inflammation and ambulatory blood pressure response to antihypertensive treatment: the ALPHABET study, Am J Hypertens, 26, 784, 10.1093/ajh/hpt024 Pietri, 2006, Relationship between low-grade inflammation and arterial stiffness in patients with essential hypertension, J Hypertens, 24, 2231, 10.1097/01.hjh.0000249701.49854.21 Weiner, 2014, Systemic inflammation and brachial artery endothelial function in the Multi-Ethnic Study of Atherosclerosis (MESA), Heart, 100, 862, 10.1136/heartjnl-2013-304893 Vasilev, 2013, Asymmetric Dimethylarginine (ADMA) and soluble vascular cell adhesion molecule 1 (sVCAM-1) as circulating markers for endothelial dysfunction in patients with pheochromocytoma, Exp Clin Endocrinol Diabetes, 121, 551, 10.1055/s-0033-1353183 Weiss, 2013, Components of the interlukin-6 transsignalling system are associated with the metabolic syndrome, endothelial dysfunction and arterial stiffness, Metabolism, 62, 1008, 10.1016/j.metabol.2013.01.019 Deanfield, 2007, Endothelial function and dysfunction: testing and clinical relevance, Circulation, 115, 1285, 10.1161/CIRCULATIONAHA.106.652859 Schiffrin, 2008, Oxidative stress, nitric oxide synthase, and superoxide dismutase: a matter of imbalance underlies endothelial dysfunction in the human coronary circulation, Hypertension, 51, 31, 10.1161/HYPERTENSIONAHA.107.103226 Angela, 2013, LOX-1, ox-LDL and atherosclerosis, Mediat Inflamm, 2013 Sies, 1997, Oxidative stress: oxidants and antioxidants, Exp Physiol, 82, 291, 10.1113/expphysiol.1997.sp004024 Nickening, 2002, The AT-1-type angiotensin receptor in oxidative stress and hypertension part I: oxidative stress and atherogenesis, Circulation, 105, 393, 10.1161/hc0302.102618 Ray, 2005, NADPH oxidase and endothelial cell function, Clin Sci, 109, 217, 10.1042/CS20050067 Ebrahimian, 2011, Mitogen-activated protein kinase-activated protein kinase 2 in angiotensin II-induced inflammation and hypertension: regulation of oxidative stress, Hypertension, 57, 245, 10.1161/HYPERTENSIONAHA.110.159889 Sies, 2007, Total antioxidant capacity: appraisal of a concept, J Nutr, 137, 1493, 10.1093/jn/137.6.1493 Wang, 2013, Plasma and dietary antioxidant status as cardiovascular disease risk factors: a review of human studies, Nutrients, 5, 2969, 10.3390/nu5082969 Mann, 2007, Nrf2/ARE regulated antioxidant gene expression in endothelial and smooth muscle cells in oxidative stress: implications for atherosclerosis and preeclampsia, Acta Phys Sin, 59, 117 Vaziri, 2008, Causal link between oxidative stress, inflammation, and hypertension, Iran J Kidney Dis, 2, 1 Cai, 2000, Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress, Circ Res, 87, 840, 10.1161/01.RES.87.10.840 Majzunova, 2013, Redox signaling in pathophysiology of hypertension, J Biomed Sci, 20, 69, 10.1186/1423-0127-20-69 Ishibashi, 2013, Molecular hydrogen: new antioxidant and anti-inflammatory therapy for rheumatoid arthritis and related diseases, Curr Pharm Des, 19, 6375, 10.2174/13816128113199990507 Ng, 2012, The role of repeatedly heated soybean oil in the development of hypertension in rats: association with vascular inflammation, Int J Exp Pathol, 93, 377, 10.1111/j.1365-2613.2012.00839.x Savoia, 2011, Vascular inflammation and endothelial dysfunction in experimental hypertension, Int J Hypertens, 2011, 1, 10.4061/2011/281240 Pacurari, 2014, The renin–angiotensin–aldosterone system in vascular inflammation and remodeling, Int J Inflamm, 2014, 1, 10.1155/2014/689360 Horio, 2014, Role of endothelial cell-derived angptl2 in vascular inflammation leading to endothelial dysfunction and atherosclerosis progression, Atheroscler Thromb Vasc Biol, 34, 790, 10.1161/ATVBAHA.113.303116 Devaraj, 2011, C-reactive protein induces release of both endothelial microparticles and circulating endothelial cells in vitro and in vivo: further evidence of endothelial dysfunction, Clin Chem, 57, 1757, 10.1373/clinchem.2011.169839 Leong, 2009, Intake of repeatedly heated palm oil causes elevation in blood pressure with impaired vasorelaxation in rats, Tohoku J Exp Med, 219, 71, 10.1620/tjem.219.71 Steyers, 2014, Endothelial dysfunction in chronic inflammatory diseases, Int J Mol Sci, 15, 11324, 10.3390/ijms150711324 Lemkens, 2012, Dual neural peptidase/endothelin-converting enzyme inhibition improves endothelial function in mesenteric resistance arteries of young spontaneously hypertensive rats, J Hypertens, 30, 1799, 10.1097/HJH.0b013e3283569c7a LaMarca, 2009, Hypertension in response to autoantibodies to the angiotensin II type I receptor (AT1-AA) in pregnant rats: role of endothelin-1, Hypertension, 54, 905, 10.1161/HYPERTENSIONAHA.109.137935 Donato, 2009, Vascular endothelial dysfunction with aging: endothelin-1 and endothelial nitric oxide synthase, Am J Physiol Heart Circ Physiol, 297, H425, 10.1152/ajpheart.00689.2008 Widyantoro, 2010, Endothelial cell-derived endothelin-1 promotes cardiac fibrosis in diabetis hearts through stimulation of endothelial-to-mesenchymal transition, Circulation, 121, 2407, 10.1161/CIRCULATIONAHA.110.938217 Barhoumi, 2014, Erythropoietin-induced hypertension and vascular injury in mice overexpressing human endothelin-1: exercise attenuated hypertension, oxidative stress, inflammation and immune response, J Hypertens, 32, 784, 10.1097/HJH.0000000000000101 Saleh, 2010, Endothelin-1 increases glomerular permeability and inflammation independent of blood pressure in the rat, Hypertension, 56, 942, 10.1161/HYPERTENSIONAHA.110.156570 Deacon, 2010, Endothelin-1 (ET-1) increases the expression of remodeling genes in vascular smooth muscle through linked calcium and cAMP pathwyas: role of phospholipase A(2)(sPLA(2))/cyclooxygenase-2 (COX-2)/prostacyclin receptor-dependent autocrine loop, J Biol Chem, 285, 25913, 10.1074/jbc.M110.139485 Sun, 2014, Endothelin-1 induces a glycolytic switch in pulmonary arterial endothelial cells via the mitochondrial translocation of endothelial nitric oxide synthase, Am J Respir Cell Mol Biol, 50, 1084, 10.1165/rcmb.2013-0187OC Kuo, 2013, Vasomotor regulation of coronary microcirculation by oxidative stress: role of arginase, Front Immunol, 4, 237, 10.3389/fimmu.2013.00237 Honavar, 2011, Chlorine gas exposure causes systemic endothelial dysfunction by inhibiting endothelial nitric oxide synthase-dependent signaling, Am J Respir Cell Mol Biol, 45, 419, 10.1165/rcmb.2010-0151OC Weldy Chad, 2011, DIESEL particulate exposed macrophages alter endothelial cell expression of eNOS, iNOS, MCP1, and glutathione synthesis genes, Toxicol in Vitro, 25, 2064, 10.1016/j.tiv.2011.08.008 Zhao, 2011, CRP enhances soluble LOX-1 release from macrophages by activating TNF-α converting enzyme, J Lipid Res, 52, 923, 10.1194/jlr.M015156 Forstermann, 2011, Therapeutic effect of enhancing endothelial nitric oxide synthase (eNOS) expression and preventing eNOS uncoupling, Br J Pharmacol, 164, 213, 10.1111/j.1476-5381.2010.01196.x Oliveira-Paula, 2014, Inducible nitric oxide synthase as a possible target in hypertension, Curr Drug Targets, 15, 164, 10.2174/13894501113146660227 Sankaralingam, 2010, Arginase contributes to endothelial cell oxidative stress in response to plasma from women with preeclampsia, Cardiovasc Res, 85, 194, 10.1093/cvr/cvp277 Ryoo, 2011, Ox-LDL-dependent activation of arginase II is dependent on the LOX-1 receptor and downstream RhoA signalling, Atherosclerosis, 214, 279, 10.1016/j.atherosclerosis.2010.10.044 Auclair, 2013, Peroxisome proliferator-activated receptor-γ mutations responsible for lipodystrophy with severe hypertension activate the cellular renin–angiotensin system, Atheroscler Thromb Vasc Biol, 33, 829, 10.1161/ATVBAHA.112.300962 Martin, 1997, Cytokine induction of monocyte chemoattractant protein-1 gene expression in human endothelial cells depends on the cooperative action of NF-χB and AP-1, Eur J Immunol, 27, 1091, 10.1002/eji.1830270508 Desai, 2012, META060 attenuates TNF-α-activated inflammation, endothelial-monocyte interactions, and matrix metalloproteinase-9 expression, and inhibits NF-κB and AP-1 in THP-1 monocytes, Atherosclerosis, 223, 130, 10.1016/j.atherosclerosis.2012.05.004 Sprague, 2009, Inflammatory cytokines in vascular dysfunction and vascular disease, Biochem Pharmacol, 78, 539, 10.1016/j.bcp.2009.04.029 Bisaillon, 2010, Essential role for STIM1/Orai 1-mediated calcium influx in PDGF-induced smooth muscle migration, Am J Physiol Cell Physiol, 298, C993, 10.1152/ajpcell.00325.2009 Carnevale, 2012, PI3Kγ inhibition reduces blood pressure by a vasorelaxant Akt/L-type calcium channel mechanism, Cardiovasc Res, 93, 200, 10.1093/cvr/cvr288 Sarmiento, 2014, Increases in reactive oxygen species enhance vascular endothelial cell migration through a mechanism dependent on the transient receptor potential melastatin 4 ion channel, Microvasc Res Yeh, 2013, Lercanidipine and labedipinedilol-A attenuate lipopolysaccharide/interferon-γ-induced inflammation in rat vascular smooth muscle cells through inhibition of HMGB1 release and MMP-2, 9 activities, Atherosclerosis, 226, 364, 10.1016/j.atherosclerosis.2012.12.005 Ledoux, 2006, Calcium-activated potassium channels and the regulation of vascular tone, Physiology, 21, 69, 10.1152/physiol.00040.2005 Yamamoto, 2008, TRPM2-mediated Ca2+ influx induces chemokine production in monocytes that aggravates inflammatory neutrophil infiltration, Nat Med, 14, 738, 10.1038/nm1758 Schepers, 2009, Role of symmetric dimethylarginine in vascular damage by increasing ROS via store-operated calcium influx in monocytes, Nephrol Dial Transplant, 24, 1429, 10.1093/ndt/gfn670 Zhang, 2010, Circulating mitochondrial DAMPs cause inflammatory responses to injury, Nature, 464, 104, 10.1038/nature08780 Li, 2013, Upregulation of heme oxygenase-1 potentiates EDH-type relaxations in the mesenteric artery of the spontaneously hypertensive rat, Am J Physiol Heart Circ Physiol, 305, H1471, 10.1152/ajpheart.00962.2012 Nagano, 2013, Apelin elevates blood pressure in ICR mice with L-NAME-induced endothelial dysfunction, Mol Med Rep, 7, 1371, 10.3892/mmr.2013.1378 Zhang, 2014, Tumor necrosis factor-α produced in the kidney contributes to Angiotensin-II-dependent hypertension, Hypertension, 64, 1275, 10.1161/HYPERTENSIONAHA.114.03863 Tinsley, 2010, Interleukin-10 reduces inflammation, endothelial dysfunction, and blood pressure inhypertensive pregnant rats, Am J Physiol Regul Integr Comp Physiol, 298, R713, 10.1152/ajpregu.00712.2009 Toma, 2011, Anti-oxidant and anti-inflammatory mechanisms of amlodipine action to improve endothelial cell dysfunction induced by irreversibly glycated LDL, Biochem Biophys Res Commun, 411, 202, 10.1016/j.bbrc.2011.06.137 Armoza, 2013, Tomato extract and the carotenoids lycopene and lutein improve endothelial function and attenuate inflammatory NF-kB signaling in endothelial cells, J Hypertens, 31, 521, 10.1097/HJH.0b013e32835c1d01 Giles, 2012, Impaired vasodilation in the pathogenesisn of hypertension: focus on nitric oxide, endothelial-derived hyperpolarizing factors, and prostaglandins, J Clin Hypertens, 14, 198, 10.1111/j.1751-7176.2012.00606.x Ozkor, 2011, Endothelium-derived hyperpolarizing factor and vascular function, Cardiol Res Pract, 1, 156146 Renna, 2013, Role of renin–angiotensin system and oxidative stress on vascular inflammation in insulin resistence model, Int J Hypertens, 2013, 1, 10.1155/2013/420979 Hayenga, 2013, Stiffness increases mononuclear cell transendothelial migration, Cell Mol Bioeng, 6, 253, 10.1007/s12195-013-0284-9 Van Bussel, 2012, Low-grade inflammation, but not endothelial dysfunction, is associated with greater carotid stiffness in the elderly: the Hoorn study, J Hypertens, 30, 744, 10.1097/HJH.0b013e328350a487 Gkaliagkousi, 2012, Elevated levels of MMP-9 in untreated patients with stage I essential hypertension, Clin Exp Hypertens, 34, 561, 10.3109/10641963.2012.681726 Goyal, 2012, Current concepts of the role of oxidized LDL receptors in atherosclerosis, Curr Atheroscler Rep, 14, 150, 10.1007/s11883-012-0228-1 Pirillo, 2013, LOX-1, ox-LDL, and atherosclerosis, Mediat Inflamm, 2013, 152786, 10.1155/2013/152786 Stein, 2010, SIRT1 decreases LOX-1-mediated foam cell formation in atherogenesis, Eur Heart J, 31, 2301, 10.1093/eurheartj/ehq107 Chen, 2010, The reciprocal relationship between adiponectin and LOX-1 in the regulation of endothelial dysfunction in ApoE knockout mice, Am J Physiol Heart Circ Physiol, 299, H605, 10.1152/ajpheart.01096.2009 Zhou, 2014, Combination therapy of amlodipine and atorvastatin has more beneficial vascular effects than monotherapy in slat-sensitive hypertension, Am J Hypertens, 27, 873, 10.1093/ajh/hpt272 Lubrano, 2014, LOX-1 and ROS, inseparable factors in the process of endothelial damage, Free Radic Res, 48, 841, 10.3109/10715762.2014.929122 Zhou, 2013, Ox-LDL downregulates eNOS activity via LOX-1-mediated endoplasmic reticulum stress, Int J Mol Med, 32, 1442, 10.3892/ijmm.2013.1513 Adam, 2008, Effects of repeatedly heated palm oil on serum lipid profile, lipid peroxidation and homocystein levels in a post-menopausal rat model, McGill J Med, 11, 145 Kenney, 2012, Cutaneous microvascular dysfunction correlates with serum LDL and sLOX-1 receptor concentrations, Microvasc Res, 85, 112 Ozyazgan, 2013, Lectin-like oxidised LDL receptor-1 as a marker of endothelial dysfunction in Bechet's disease, Clin Exp Rheumatol, 31, 71 Goncalves, 2012, Evidence supporting a key role of Lp-PLA2-generated lypophosphatidylcholine in human atherosclerotic plaque inflammation, Atheroscler Thromb Vasc Biol, 32, 1505, 10.1161/ATVBAHA.112.249854 Racherla, 2012, Utility of Lp-PLA2 in lipid-lowering therapy, Am J Ther, 19, 115, 10.1097/MJT.0b013e3181e70d32 Borsch-Haubold, 1998, Direct inhibition of cyclooxygenase −1 and −2 by the kinase inhibitors SB 203580 and PD 98059 SB 203580 also inhibits thromboxane synthase, J Biol Chem, 273, 28766, 10.1074/jbc.273.44.28766 Dileep, 2012, Binding to PLA2 may contribute to the anti-inflammatory activity of cathecol, Chem Biol Drug Des, 79, 143, 10.1111/j.1747-0285.2011.01258.x Mendes, 2012, Selective inhibition of cyclooxygenase-2: risks and benefits, Rev Bras Reumatol, 52, 767 Toniolo, 2013, Cyclooxygenase-1 and prostacyclin production by endothelial cells in the presence of mild oxidative stress, PLoS ONE, 8, e56683, 10.1371/journal.pone.0056683 Kirby, 2012, Cyclooxygenase-1, not cyclooxygenase-2, is responsible for physiological productionof prostacyclin in the cardiovascular system, PNAS, 109, 17597, 10.1073/pnas.1209192109 Davi, 2007, Mechanisms of disease: platelet activation and atherothrombosis, N Engl J Med, 357, 2482, 10.1056/NEJMra071014 Buie, 2014, Role of interferon alpha in endothelial dysfunction: insights into endothelial nitric oxide synthase-related mechanisms, Am J Med Sci, 348, 168, 10.1097/MAJ.0000000000000284 Sedeek, 2009, Molecular mechanisms of hypertension: role of Nox family NADPH oxidases, Curr Opin Nephrol Hypertens, 18, 122, 10.1097/MNH.0b013e32832923c3 Munzel, 2010, Is oxidative stress a therapeutic target in cardiovascular disease?, Eur Heart J, 31, 2741, 10.1093/eurheartj/ehq396 Jasinska, 2007, Statins: a new insight into teir mechanisms of action and consequent pleiotropic effects, Pharmacol Rep, 59, 483 Taguchi, 2013, Irbesartan, an angiotensin receptor blocker, exhibit metabolic, anti-inflammatory and antioxidative effects in patients with high-risk hypertension, Hypertens Res, 36, 608, 10.1038/hr.2013.3 Halliwell, 2007 Litescu, 2010, Methods for determination of antioxidant capacity in food and raw materials, 698(18), 241 Flores-Mateo, 2006, Selenium and coronary heart disease: a meta-analysis, Am J Clin Nutr, 84, 762, 10.1093/ajcn/84.4.762 Nishi, 2010, Vitamin C prevents DNA damage induced by renovascular hypertension in multiple organs of Wistar rats, Hum Exp Toxicol, 29, 593, 10.1177/0960327109358267 Botelho-Ono, 2011, Acute superoxide scavenging restores depressed baroreflex sensitivity in renovascular hypertensive rats, Auton Neurosci, 159, 38, 10.1016/j.autneu.2010.07.025 Bruno, 2012, Effect of acute administration of vitamin C on muscle sympathetic activity, cardiac sympathovagal balance, and baroreflex sensitivity in hypertensive patients, Am J Clin Nutr, 96, 302, 10.3945/ajcn.112.035022 Albaghdadi, 2007, Baroreflex control of long-term arterial pressure, Rev Bras Hipertens, 14, 212 Yamazaki, 2012, Oral vitamin C enhances the adrenergic vasoconstrictor response to local cooling in human skin, J Appl Physiol, 112, 1689, 10.1152/japplphysiol.00043.2012 Esmaeilpour-Bezenjani, 2013, Effect of administration of ascorbic acid and dopamine D2 receptors agonist in the hippocampal CA1 area on spatial learning and memory in adult male rats, Iran J Vet Res, 14, 126 Chelazzi, 2011, Postoperative Atrial Fibrillation, 2011 Uzun, 2013, Does vitamin C or its combination with vitamin e improve radial artery endothelium-dependent vasodilatation in patients awaiting coronary artery bypass surgery?, Cardiovasc J Afr, 24, 255, 10.5830/CVJA-2013-046 May, 2013, Role of vitamin C in the function of the vascular endothelium, Antioxid Redox Signal, 19, 2068, 10.1089/ars.2013.5205 Carr, 2013, Synthetic or food-derived vitamin C-Are they equally bioavailable?, Nutrients, 5, 4284, 10.3390/nu5114284 Agarwal, 2012, Differing relations to early atherosclerosis between vitamin C from supplements vs. food in the Los Angeles atherosclerosis study: a prospective cohort study, Open Cardiovasc Med J, 6, 113, 10.2174/1874192401206010113 Loke, 2010, Specific dietary polyphenols attenuate atherosclerosis in apolipoprotein e-knockout mice by alleviating inflammation and endothelial dysfunction, Atheroscler Thromb Vasc Biol, 30, 749, 10.1161/ATVBAHA.109.199687 Scoditti, 2012, Mediterranean diet polyphenols reduce inflammatory angiogenesis through MMP-9 and COX-2 inhibition in human vascular endothelial cells: a potentially protective mechanism in atherosclerotic vascular disease and cancer, Arch Biochem Biophys, 527, 81, 10.1016/j.abb.2012.05.003 Mukai, 2011, Polyphenol-containing azuki bean (Vigna angularis) seed coats attenuate vascular oxidative stress and inflammation in spontaneously hypertensive rats, J Nutr Biochem, 22, 16, 10.1016/j.jnutbio.2009.11.004 Natsume, 2014, Suppressive effects of cacao polyphenols on the development of atherosclerosis in apolipoprotein E-deficient mice, Subcell Biochem, 77, 189, 10.1007/978-94-007-7920-4_16 Cuevas, 2014, Identification of microRNAs involved in the modulation of pro-angiogenic factors in atherosclerosis by a polyphenol-rich extract from propolis, Arch Biochem Biophys, 557, 28, 10.1016/j.abb.2014.04.009 Widmer, 2013, Beneficial effects of polyphenol-rich olive oil in patients with early atherosclerosis, Eur J Nutr, 52, 1223, 10.1007/s00394-012-0433-2 Botden, 2012, Red wine polyphenols do not lower peripheral or central blood pressure in high normal blood pressure and hypertension, Am J Hypertens, 25, 718, 10.1038/ajh.2012.25 Ras, 2013, Effect of polyphenol-rich grape seed extract on ambulatory blood pressure in subjects with pre- and stage I hypertension, Br J Nutr, 110, 2234, 10.1017/S000711451300161X Da Costa, 2012, Euterpe oleracea Mart-derived polyphenols prevent endothelial dysfunction and vascular structural changes in renovascular hypertensive rats: role of oxidative stress, Naunyn Schmiedeberg's Arch Pharmacol, 385, 1199, 10.1007/s00210-012-0798-z Hou, 2012, Effect of the flavonoid fraction of Lithocarpus polystachyus Rehd on spontaneously hypertensive and normotensive rats, J Ethnopharmacol, 143, 441, 10.1016/j.jep.2012.06.016 Li, 2012, Effect of total flavonoids in Apocynum venetum leaves on rat hypertension induced by high fat and high salt and its molecular mechanism, Chin Tradit Herb Drugs, 43, 540 Harari, 2013, Prevention of atherosclerosis progression by 9-cis-β-carotene rich alga dunaliella in apoE-deficient mice, Biomed Res Int, 2013, 169517, 10.1155/2013/169517 Meydani, 2014, Long-term vitamin E supplementation reduces atherosclerosis and mortality in Ldlr−/− mice, but not when fed Western style diet, Atherosclerosis, 233, 196, 10.1016/j.atherosclerosis.2013.12.006 Boni, 2010, Antioxidant vitamins and prevention of atherosclerosis in childhood, Rev Paul Pediatr, 28, 373, 10.1590/S0103-05822010000400014 Bozaykut, 2014, Effects of vitamin E on peroxisome proliferator-activated receptor γ and nuclear factor-erythroid 2-related factor 2 in hypercholesterolemia-induced atherosclerosis, Free Radic Biol Med, 70, 174, 10.1016/j.freeradbiomed.2014.02.017 Che Idris, 2014, Oil palm phenolics and vitamin E reduce atherosclerosis in rabbits, J Funct Foods, 7, 541, 10.1016/j.jff.2014.01.002 Rasool, 2006, Dose dependent elevation of plasma tocotrienol levels and its effect on arterial compliance, plasma total antioxidant status, and lipid profile in healthy humans supplemented with tocotrienol rich vitamin E, J Nutr Sci Vitaminol, 52, 473, 10.3177/jnsv.52.473 Young, 2001, Measurement of total antioxidant capacity, J Clin Pathol, 54, 339, 10.1136/jcp.54.5.339 Weydert, 2010, Measurement of superoxide dismutase, catalase and glutathione peroxidase in cultured cells and tissue, Nat Protoc, 5, 51, 10.1038/nprot.2009.197 Mahajan, 2007, Antihypertensive and antioxidant action of amlodipine and vitamin C in patients of essential hypertension, J Clin Biochem Nutr, 40, 141, 10.3164/jcbn.40.141 Rodrigo, 2008, Decrease in oxidative stress through supplementation of vitamins C and E is associated with a reduction in blood pressure in patients with essential hypertension, Clin Sci, 114, 625, 10.1042/CS20070343 Plantinga, 2007, Supplementation with vitamins C and E improves arterial stiffness and endothelial function in essential hypertensive patients, Am J Hypertens, 20, 392, 10.1016/j.amjhyper.2006.09.021 Milman, 2008, Vitamin E supplementation reduces cardiovascular events in a subgroup of middle-aged individuals with both type 2 diabetes mellitus and the haptoglobin 2–2 genotype: a prospective double-blinded clinical trial, Arterioscler Thromb Vasc Biol, 28, 341, 10.1161/ATVBAHA.107.153965 Shargorodsky, 2010, Effect of long-term treatment with antioxidants(vitamin C, vitamin E, coenzyme Q10 and selenium)on arterial compliance, humoral factors and inflammatory markers in patients with multiple cardiovascular risk factors, Nutr Metab, 7, 55, 10.1186/1743-7075-7-55 Hawkes, 2009, Selenium supplementation does not improve vascular responsiveness in healthy North American men, Am J Physiol Heart Circ Physiol, 296, H256, 10.1152/ajpheart.00935.2008 Edwards, 2007, Quercetin reduces blood pressure in hypertensive subjects, J Nutr, 137, 2405, 10.1093/jn/137.11.2405 Cook, 2007, A randomized factorial trial of vitamins c, e, and beta-carotene in the secondary prevention of cardiovascular events in women: results from the Women's Antioxidant Cardiovascular Study (WACS), Arch Intern Med, 167, 1610, 10.1001/archinte.167.15.1610 Sesso, 2008, Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized trial, JAMA, 300, 2123, 10.1001/jama.2008.600 Belch, 2008, The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease, BMJ, 337, a1840, 10.1136/bmj.a1840 Kidd, 2009, Bioavailability and activity of phytosome complexes from botanical polyphenols: the silymarin, curcumin, green tea, and grape seed extract, Altern Med Rev, 14, 226 McCullough, 2012, Flavonoid intake and cardiovascular disease mortality in a prospective cohort of US adults, Am J Clin Nutr, 95, 454, 10.3945/ajcn.111.016634 Mink, 2007, Flavonoid intake and cardiovascular disease mortality: a prospective study in postmenopausal women, Am J Clin Nutr, 85, 895, 10.1093/ajcn/85.3.895 Mursu, 2008, Flavonoid intake and the risk of ischaemic stroke and CVD mortality in middle-aged Finnish men: the Kuopio Ischaemic Heart Disease Risk Factor Study, Br J Nutr, 100, 890, 10.1017/S0007114508945694 Lin, 2007, Dietary intakes of flavonols and flavones and coronary heart disease in US women, Am J Epidemiol, 165, 1305, 10.1093/aje/kwm016 Buijsse, 2008, Both a- and b carotene, but not tocopherols and vitamin C, are inversely related to 15-year cardiovascular mortality in Dutch elderly men, J Nutr, 138, 344, 10.1093/jn/138.2.344 Del Rio, 2011, Total antioxidant capacity of the diet is associated with lower risk of ischemic stroke in a large Italian cohort, J Nutr, 141, 118, 10.3945/jn.110.125120 Rautiainen, 2012, Total antioxidant capacity of diet and risk of stroke: a population-based prospective cohort of women, Stroke, 43, 335, 10.1161/STROKEAHA.111.635557