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研究生:李博仁
研究生(外文):Bor-Jen Lee
論文名稱:輔酶Q10與冠狀動脈心臟病人的抗氧化能力及發炎狀態的關係
論文名稱(外文):Coenzyme Q10 Associated with Antioxidant Capacities and Inflammatory Status in Patients with Coronary Artery Disease
指導教授:黃怡嘉黃怡嘉引用關係
學位類別:博士
校院名稱:中山醫學大學
系所名稱:營養學研究所
學門:醫藥衛生學門
學類:營養學類
論文種類:學術論文
論文出版年:2013
畢業學年度:101
語文別:英文
論文頁數:97
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台灣衛生署公告101年國人死亡原因心臟、腦血管及高血壓等心血管疾病在十大死因中,為第2位僅次於惡性腫瘤。已知造成心血管疾病的原因主要來自血管的病變和動脈粥狀硬化,嚴重時會引發血管狹窄、缺血,續引發冠狀動脈心臟病(coronary artery disease; CAD)、心臟衰竭、中風等致死等的併發症。動脈粥狀硬化為CAD主要成因,形成過程複雜,其致病機轉涉及脂質代謝異常、氧化壓力及炎症反應。因此預防及治療動脈粥狀硬化為醫療上很重要的議題。
輔酶Q10(coenzyme Q10 亦稱為Ubiquinone)為一種內生性親脂溶性的抗氧化物質,是參與粒線體氧化磷酸反應及電子傳遞鏈(electron transport chain)產生能量-ATP之必須輔助因子(essential cofactor)。已有臨床實驗證實對罹患高血壓、心臟衰竭及心臟手術病人,使用補充輔酶Q10可以顯著改善其心臟功能, 增進運動耐受性及縮短手術後恢復時間。
本研究探討CAD之病人其抗氧化活性、發炎狀態與輔酶Q10血中濃度之關係,輔酶Q10濃度與罹患CAD之相關性,並接受高劑量輔酶Q10補充劑後,對於抗氧化酵素活性與發炎反應之效應。以期提供積極預防及治療CAD之依循。
此研究共募集51位CAD病人及102位健康受試者,測量其血壓、血中脂質、脂質過氧化物(MDA丙二醛)、抗氧化酵素 [ 超氧化物歧化酶( SOD )、過氧化氫酶( CAT )及麩胱甘肽過氧化酶 (GPx)] 活性與發炎指標[ 超敏感C-反應性蛋白腫( hs-CRP )、介白素-6 ( IL-6)、同半胱胺酸]。追蹤51位CAD病人受試者接受隨機分派後,分別給予輔酶Q10補充劑 (60mg/天,n = 19) 或高輔酶Q10補充劑(150mg/天,n = 18),持續3個月。
結果顯示CAD病人之輔酶Q10、CAT、SOD、GPx濃度皆比健康受試者有顯著下降,MDA濃度顯著高於健康受試者。但調整CAD 危險因子後,SOD 活性對血漿輔酶Q10濃度有顯著之負相關性。當血漿輔酶Q10(≧0.52 μM)時會顯著降低罹患CAD 之危險對比值( OR, 0.08; 95% CI,0.02-0.36)。完成研究43位CAD之受試者,在輔酶Q10補充劑組(150 mg/d)之血漿輔酶Q10濃度於第4週起持續顯著上升 (P < 0.01)。在第8週MDA濃度有顯著降低(P = 0.03)。在第12週CAT、SOD濃度有顯著上升(P = 0.03;SOD,P = 0.03),及IL-6濃度顯著降低(P = 0.03)。同時輔酶Q10與GPx和同型半胱氨酸之間無相關性。
此研究結果顯示血漿輔酶Q10≧0.52 μM 可顯著降低罹患CAD 之風險,高劑量的輔酶Q10補充劑(150毫克/天)介入可以減少CAD病人的MDA濃度和提高SOD、CAT活性, 並減少發炎指標IL-6。因此高劑量的輔酶Q10補充劑可促進CAD病人者的抗氧化與抗發炎等反應。


According to the statistics of Department of Health, R.O.C. (TAIWAN), cardiovascular disease rate of the standardized mortality, has been the second cause-of-death behind cancer among the top 10 in 2012. Cardiovascular disease (CVD) including coronary artery disease (CAD), congestive heart failure, cardiomyopathy, stroke and other fatal complications. Atherosclerosis is the main cause of CAD, The pathogenesis of atherosclerosis involves a complex series of events, as abnormal lipid metabolism, oxidative stress and chronic inflammatory process, with the formation of atherosclerotic plaque as the end result. Therefore the prevention and treatment of atherosclerosis is important topics in medical healthcare.
Coenzyme Q10 (ubiquinone) is a lipid-soluble anti-oxidant with cell protective effect, also plays as an essential cofactor in mitochondrial oxidative phosphorylation and ATP production. In clinical trial, the supplementation of Q10 as an adjunct to conventional therapy in patients with congestive heart failure, cardiomyopathy and ishemic cardiac surgery shows that it can afford significant clinical benefit in exercise tolerance, heart function and reducing recovery period.
The aim of this study was to investigate the relationship of antioxidant enzyme activities and inflammatory status with CQ10 concentration in patient with coronary artery disease, and calculate the odds ratio of coronary artery disease with the CQ10 concentration. Furthermore, this study was to investigate the effects of CoQ10 supplementation in response to antioxidant enzyme activity and inflammatory status in patients with coronary artery disease.
Patient who were identified by cardiac catheterization as having at least 50% stenosis of one major coronary artery were assigned to case group (n = 51) and healthy participated was assigned to the control group (n = 102) in this study. Hematologic profiles, plasma CoQ10, malondialdehyde (MDA), antioxidant enzyme activity: superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and inflammatory markers [ High-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and homcysterine] were measured. Fitty-one subjects with CAD (47 males/ 4 females) were randomly assigned to one of three groups: a placebo group (n = 14), or one of two CoQ10 groups (60 mg/d, n = 19 [Q10-60] group; 150 mg/d, n = 18 [Q10-150]) group] and intervention for 12 weeks. Forty-three subjects with CAD completed the intervention study. The result showed that CoQ10 concentration, CAT, SOD and GPx enzyme activities were significantly lower than healthy participants, MDA was significantly higher than healthy participant. The Plasma Q10 concentration and SOD had statistically significant negative correlation after adjusted CAD confounders. Plasma Q10 concentration (≧0.52 μM) had a significant association with decreased risk of CAD (OR, 0.08; 95% CI, 0.02-0.36). After 12 week of Q10 supplementation, the results show plasma CoQ10 concentration were significantly increased after supplementation in the Q10-150 group (P < 0.01) at week 4. The MDA levels were significantly lower than placebo at week 8 (P = 0.03). At the week 12, the antioxidant enzyme activities of CAT (P = 0.03) and SOD (P = 0.03) were significantly higher than placebo but also the inflammatory marker IL-6 (P = 0.03) were significantly lower than the placebo, too. However, there was not relationship between CoQ10 concentration and GPx activity or homocysteine.
In conclusion, Plasma Q10 concentration (≧0.52 μM) had a significantly association with lower risk of CAD. In addition, high dose of CoQ10 supplementation ( 150 mg / day) intervention have a significantly increase CoQ10 concentration and anti-oxidant enzyme activities (SOD, CAT ) and have a significantly lower MDA and IL-6 concentration, Therefore higher dosage of Q10 supplementation may benefit patients with CAD by anti-oxidative and anti-inflammatory activities.


TABLE OF CONTENTS
中文摘要..................................................1
Abstract..................................................3
Literature Review.........................................5
Introduction..............................................6
Biochemistry of Oxidative Stress..........................7
Oxidative Stress and Antioxidants in Experimental Models of CVD.......................................................9
Cardiovascular Disease in Relation to Inflammation.......12
Roles of Coenzyme Q10 in Mitochondrial ATP and ROS Production...............................................13
Antioxidant Effects of Coenzyme Q10 on Lipids............15
Anti-inflammatory Property of Coenzyme Q10...............16
Coenzyme Q10 and Endothelial Function....................17
Coenzyme Q10 Deficiency and Cardiovascular disease.......19
Coenzyme Q10 Administration in Relation to Cardiovascular Disease..................................................20
Coenzyme Q10 and Coronary Artery Disease.................22
HMG CoA-reductase Inhibitors (Statins) and Coenzyme Q10..24
References...............................................27
Purposes.................................................38
Motivation and purposes of PART I:.......................39
PART I The Relationship between Coenzyme Q10, Oxidative Stress, and Antioxidant Enzymes Activities and Coronary Artery Disease...........................................40
1-1. Abstract............................................41
1-2. Introduction........................................42
1-3. Materials and Methods...............................43
1-4. Result..............................................45
1-5. Discussion and Conclusion...........................46
1-6. Tables..............................................49
1-7. Figures.............................................52
1-8. References..........................................54

Motivation and purposes of PART II & III.................57
PART II Coenzyme Q10 Supplementation Reduces Oxidative Stress and Increases Antioxidant Enzyme Activity in Patients with Coronary Artery Disease....................58
2-1. Abstract............................................59
2-2. Introduction........................................60
2-3. Materials and methods...............................61
2-4. Laboratory analyses:................................62
2-5. Statistical analyses................................63
2-6. Results.............................................64
2-7. Discussion..........................................65
2-8. Figures.............................................67
2-9. Tables..............................................69
2-10. References.........................................71
PART III Effects of Coenzyme Q10 Supplementation on Inflammatory Markers (High-sensitivity C-reactive protein, Interleukin-6, and Homocysteine) in Patients with Coronary Artery Disease...........................................75
3-1. Abstract............................................76
3-2. Introduction........................................77
3-3. Materials and methods...............................78
3-4. Study protocol......................................79
3-5. Laboratory analyses.................................80
3-6. Statistical analyses................................81
3-7. Results.............................................82
3-8. Discussion..........................................83
3-9. Figures.............................................85
3-10. Tables.............................................87
3-11.References..........................................90
Limitation...............................................93
Anticipation and Foresight...............................94
Appendixes...............................................95
Appendix 1 Informed Consent..............................96
Appendix 2 Approval of Institutional Review board of Taichung Veterans General Hospital.......................97

References

[1]Dusting GJ & Triggle C. Are we over oxidized? Oxidative stress, cardiovascular disease, and the future of intervention studies with antioxidants. Vasc Health Risk Manag 2005; 1: 93-97.
[2]Lawlor DA, Davey Smith G, Kundu D, Bruckdorfer KR, Ebrahim S. Those confounded vitamins: what can we learn from the differences between observational versus randomized trial evidence? Lancet 2004; 363: 1724–1727.
[3]Lonn E. Dose response of ACE inhibitors: Implications of the SECURE trial. Curr Control Trials Cardiovasc Med 2001; 2: 155–159.
[4]Morris DL, Kritchevsky SB, Davis CE. Serum carotenoids and coronary heart disease. The Lipid Research Clinics Coronary Primary Prevention Trial and Follow-up Study. JAMA 1994; 272: 1439–1441.
[5]Rimm EB, Stampfer MJ, Ascherio A, Giovannucci E, Colditz GA, Willett WC. Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med 1993; 328: 1450–1456.
[6]Niwa K, Inanami O, Yamamori T, et al. Roles of protein kinase C delta in the accumulation of P53 and the induction of apoptosis in H2O2-treated bovine endothelial cells. Free Radic Res 2002; 36: 1147–1153.
[7]Taniyama Y, Griendling KK. Reactive oxygen species in the vasculature: Molecular and cellular mechanisms. Hypertension 2003; 42: 1075–1081.
[8]Turko IV, Marcondes S, Murad F. Diabetes-associated nitration of tyrosine and inactivation of succinyl-CoA: 3-oxoacid CoA-transferase. Am J Physiol Heart Circ Physiol 2001; 281: H2289–2294.
[9]Witztum JL. The oxidation hypothesis of atherosclerosis. Lancet 1994; 344: 793–795.
[10]Taran F & James J (2000) HOPE Study Investigators. Vitamin E supplementation and cardiovascular events in high risk patients. N Engl J Med 2000; 342:154-60.
[11]Eidelman RS, Hollar D, Hebert PR, Lamas GA, Hennekens CH. Randomized trials of vitamin E in the treatment and prevention of cardiovascular disease. Arch Intern Med 2004; 164: 1552–1556.
[12]Maritim AC, Sanders RA, Watkins JB, III. Diabetes, oxidative stress, and antioxidants: A review. J Biochem Mol Toxicol 2003; 17:24–38.
[13]Evans JL, Goldfine ID, Maddux BA, Grodsky GM. Oxidative stress and stress-activated signaling pathways: A unifying hypothesis of type 2 diabetes. Endocrinol Rev 2002; 23: 599–622.
[14]Bian K, Murad F. Nitric oxide (NO) — biogeneration, regulation, and relevance to human diseases. Front Biosci 2003; 8:d264–278.
[15]Evans JL, Goldfine ID, Maddux BA, Grodsky GM. Are oxidative stress-activated signaling pathways mediators of insulin resistance and β-cell dysfunction? Diabetes 2003; 52: 1–8.
[16]Vega-Lopez S, Devaraj S, Jialal I. Oxidative stress and antioxidant supplementation in the management of diabetic cardiovascular disease. J Invest Med 2004; 52: 24–32.
[17]Rosenson RS. Statins in atherosclerosis: Lipid-lowering agents with antioxidant capabilities. Atherosclerosis 2004; 173: 1–12.
[18]Schiffrin EL, Touyz RM. From bedside to bench to bedside: Role of renin-angiotensin-aldosterone system in remodeling of resistance arteries in hypertension. Am J Physiol Heart Circ Physiol 2004; 287: H435–446.
[19]Takemoto M, Liao JK. Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors. Arterioscler Thromb Vasc Biol 2001; 21: 1712–1719.
[20]Touyz RM. Reactive oxygen species, vascular oxidative stress, and redox signaling in hypertension: What is the clinical significance? Hypertension 2004; 44: 248–252.
[21]Touyz RM, Yao G, Viel E, Amiri F, Schiffrin EL. Angiotensin II and endothelin-1 regulate MAP kinases through different redox-dependent mechanisms in human vascular smooth muscle cells. J of Hypertension 2004; 22: 1141–1149.
[22]Varin R, Mulder P, Tamion F, et al. Improvement of endothelial function by chronic angiotensin-converting enzyme inhibition in heart failure: Role of nitric oxide, prostanoids, oxidant stress, and bradykinin. Circulation 2000; 102: 351–356.
[23]Green K, Brand MD, Murphy MP. Prevention of mitochondrial oxidative damage as a therapeutic strategy in diabetes. Diabetes 2004; 53: S110–118.
[24]Griendling KK, FitzGerald GA. Oxidative stress and cardiovascular injury: Part I: Basic mechanisms and in vivo monitoring of ROS. Circulation 2003; 08: 1912–1916.
[25]Hilenski LL, Clempus RE, Quinn MT, Lambeth JD, Griendling KK. Distinct subcellular localizations of Nox1 and Nox4 in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 2004; 24: 677–683.
[26]Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001; 414: 813–820.
[27]Nishikawa T, Edelstein D, Du XL, et al. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 2000; 404: 787–790.
[28]Boullier A, Bird DA, Chang MK, et al. Scavenger receptors, oxidized LDL, and atherosclerosis. Ann NY Acad Sci 2001; 947:214–222; discussion 222–213.
[29]Griendling KK, Sorescu D, Ushio-Fukai M. NAD (P)H oxidase: Role in cardiovascular biology and disease. Circ Res 2000; 86: 494–501.
[30]Galis ZS, Muszynski M, Sukhova GK, et al. Cytokine-stimulated human vascular smooth muscle cells synthesize a complement of enzymes required for extracellular matrix digestion. Circ Res 1994; 75: 181–189.
[31]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: 2493–2503.
[32]Griendling KK, FitzGerald GA. Oxidative stress and cardiovascular injury: Part II: Animal and human studies. Circulation 2003; 108: 2034–2040.
[33]Soriano FG, Virag L, Szabo C. Diabetic endothelial dysfunction: Role of reactive oxygen and nitrogen species production and poly (ADP-ribose) polymerase activation. J Mol Med 2001; 79: 437–448.
[34]Kunsch C, Medford RM. Oxidative stress as a regulator of gene expression in the vasculature. Circ Res 1999; 85: 753–766.
[35]Hensley K, Robinson KA, Gabbita SP, Salsman S, Floyd RA. Reactive oxygen species, cell signaling, and cell injury. Free Radic Biol Med 2000; 28: 1456–1462.
[36]Hensley K, Benaksas EJ, Bolli R, et al. New perspectives on vitamin E: α-tocopherol and carboxyethylhydroxychroman metabolites in biology and medicine. Free Radic Biol Med 2004; 36: 1–15.
[37]Hodgson JM, Watts GF. Can coenzyme Q10 improve vascular function and blood pressure? Potential for effective therapeutic reduction in vascular oxidative stress. Biofactors 2003; 18: 129–136.
[38]Hodgson JM, Watts GF, Playford DA, Burke V, Croft KD. Coenzyme Q10 improves blood pressure and glycaemic control: A controlled trial in subjects with type 2 diabetes. Eur J Clin Nutr 2002; 56: 1137–1142.
[39]Watts GF, Playford DA, Croft KD, Ward NC, Mori TA, Burke V. Coenzyme Q10 improves endothelial dysfunction of the brachial artery in Type II diabetes mellitus. Diabetologia 2002; 45: 420–426.
[40]Heller R, Unbehaun A, Schellenberg B, Mayer B, Werner-Felmayer G, Werner ER. L-ascorbic acid potentiates endothelial nitric oxide synthesis via a chemical stabilization of tetrahydrobiopterin. J Biol Chem 2001; 276: 40–47.
[41]Napoli C, Witztum JL, Calara F, de Nigris F, Palinski W. Maternal hypercholesterolemia enhances atherogenesis in normocholesterolemic rabbits, which is inhibited by antioxidant or lipid-lowering intervention during pregnancy: An experimental model of atherogenic mechanisms in human fetuses. Circ Res 2000; 87: 946–952.
[42]Ozer NK, Sirikci O, Taha S, San T, Moser U, Azzi A. Effect of vitamin E and probucol on dietary cholesterol-induced atherosclerosis in rabbits. Free Radic Biol Med 1998; 24: 226–233.
[43]Jacobsson LS, Yuan XM, Zieden B, Olsson AG. Effects of α-tocopherol and astaxanthin on LDL oxidation and atherosclerosis in WHHL rabbits. Atherosclerosis 2004; 173: 231–237.
[44]Shaish A, George J, Gilburd B, Keren P, Levkovitz H, Harats D. Dietary β-carotene and α-tocopherol combination does not inhibit atherogenesis in an ApoE-deficient mouse model. Arterioscler Thromb Vasc Biol 1999; 19: 1470–1475.
[45]Nunes GL, Robinson K, Kalynych A, King SB, 3rd, Sgoutas DS, Berk BC. Vitamins C and E inhibit O2 production in the pig coronary artery. Circulation 1997; 96: 3593–3601.
[46]Midaoui, Adil EL; de Champlain J. Prevention of hypertension, insulin resistance, and oxidative stress by α-lipoic acid. Hypertension 2002; 39: 303–307.
[47]Midaoui AE, Wu R, de Champlain J. Prevention of hypertension, hyperglycemia and vascular oxidative stress by aspirin treatment in chronically glucose-fed rats. J Hypertens 2002; 20: 1407–1412.
[48]Midaoui AE, Elimadi A, Wu L, Haddad PS, de Champlain J. Lipoic acid prevents hypertension, hyperglycemia, and the increase in heart mitochondrial superoxide production. Am J Hypertens 2003; 16: 173–179.
[49]Vasdev S, Gill V, Longerich L, Parai S, Gadag V. Salt-induced hypertension in WKY rats: prevention by α-lipoic acid supplementation. Mol Cell Biochem 2003; 254: 319–326.
[50]Mervaala E, Finckenberg P, Lapatto R, et al. Lipoic acid supplementation prevents angiotensin II-induced renal injury. Kidney Int 2003; 64: 501–508.
[51]Touyz RM. Reactive oxygen species and angiotensin II signaling in vascular cells—implications in cardiovascular disease. Braz J Med Biol Res 2004; 37: 1263–1273.
[52]Touyz RM, Schiffrin EL. Reactive oxygen species in vascular biology: Implications in hypertension. Histochem Cell Biol 2004; 122: 339–352.
[53]Warnholtz A, Nickenig G, Schulz E, et al. Increased NADH-oxidase-mediated superoxide production in the early stages of atherosclerosis: Evidence for involvement of the renin-angiotensin system. Circulation 1999; 99: 2027–2033.
[54]Braunwald E. Shattuck Lecture—cardiovascular medicine at the turn of the millennium: triumphs, concerns, and opportunities. N Engl J Med 1997; 337: 1360–1369.
[55]Kuller LH, Tracy RP, Shaten J, Meilahn EN MRFIT Research Group. Relation of C-reactive protein and coronary heart disease in MRFIT nested case–control study Am J Epidemiol 1996 Sep 15; 144: 537-547.
[56]Wu JT. Circulating homocysteine is an inflammation marker and a risk factor of life-threatening inflammatory diseases J Biomed Lab Sci 2007; 16: 107–112.
[57]Heinrich PC, Castell JV, Andus T Interleukin-6 and the acute phase response Biochem J 1990; 265: 621–636.
[58]Fuller B, Smith D, Howerton A, Kern D. Anti-inflammatory effects of CoQ10 and colorless carotenoids J Cosmet Dermatol 2006; 5: 30–38.
[59]Schmelzer C, Lorenz G, Lindner I, Rimbach G, Niklowitz P, Menke T, Doring F. Effects of Coenzyme Q10 on TNF-alpha secretion in human and murine monocytic cell lines. Biofactors 2007; 31: 35–41.
[60]Wang XL, Rainwater DL, Mahaney M.C, Stocker R. Cosupplementation with vitamin E and coenzyme Q10 reduces circulating markers of inflammation in baboons Am J Clin Nutr 2004; 80: 649–655.
[61]Kunitomo M, Yamaguchi Y, Kagota S, Otsubo K. Beneficial effect of coenzyme Q10 on increased oxidative and nitrative stress and inflammation and individual metabolic components developing in a rat model of metabolic syndrome J Pharmacol Sci 2008 Jun;107: 128-137.
[62]Shargorodsky M, Debby O, Matas Z, Zimlichman R. 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 2010; 7: 55–62.
[63]Gökbel H, Gergerlioğlu HS, Okudan O, Gül I, Büyükbaş S, Belviranli M Effects of coenzyme Q10 supplementation on plasma adiponectin, interleukin-6, and tumor necrosis factor-alpha levels in men J Med Food 2010; 13: 216–218.
[64]Green DE & Tzagoloff A. The mitochondrial electron transfer chain. Archives of Biochemistry and Biophysics 1966; 116: 293–304.
[65]Kröger A & Klingenberg M. The kinetics of the redox reactions of ubiquinone related to the electron-transport activity in the respiratory chain. European Journal of Biochemistry 1973; 34: 358–368.
[66]Estornell E, Fato R, Castelluccio C, Cavazzoni M, Parenti Castelli G, Lenaz G. Saturation kinetics of coenzyme Q in NADH and succinate oxidation in beef heart michondria. FEBS Letters 1992; 311: 107–109.
[67]Naini A, Lewis VJ, Hirano M & DiMauro S. Primary coenzyme Q10 deficiency. BioFactors 2003; 18: 145–152.
[68]Mortensen SA. Overview on coenzyme Q10 as adjunctive therapy in chronic heart failure. Rationale, design and end-points of ‘‘Q-Symbio’’ – a multinational trial. BioFactors 2003; 18: 79–89.
[69]Stocker R, Bowry VW, & Frei B. 1991 Ubiquinol-10 protects human low density lipoprotein more efficiently against lipid peroxidation than does α-tocopherol. Proceedings of the National Academy of Sciences of the USA 1991; 88: 1646–1650.
[70]Mohr D, Bowry VW, & Stocker R. Dietary supplementation with coenzyme Q10 results in increased levels of ubiquinol-10 within circulating lipoproteins and increased resistance of human low-density lipoprotein to the initiation of lipid peroxidation. Biochimica et Biophysica Acta 1992; 1126: 247–254.
[71]Yokoyama H, Lingle DM, Crestanello JA, Kamelgard J, Kott BR, Momeni R, et al. Coenzyme Q10 protects coronary endothelial function from ischemia reperfusion injury via an antioxidant effect. Surgery 1996; 120: 189–196.
[72]Kato T & Yoneda S. Reduction in blood viscosity by treatment with coenzymeQ10 in patients with ischemic heart disease. Int J Clin Pharmacol Ther Toxicol 1990; 28: 123–126.
[73]Littarru GP & Tiano L. Bioenergetic and antioxidant properties of coenzyme q10: recent developments. Mol Biotechnol 2007; 37: 31–37.
[74]Kumar A, Kaur H, & Mohan V. Coenzyme Q10 in isolated diastolic heart failure in hypertrophic cardiomyopathy (HCM).2007 The 5th Conference of the International Coenzyme Q10 Association, Kobe Japan.
[75]Kumar A, Singh RB, Saxena M, Mohammad NA, Joshi SR, Chattopadhyay P, et al. Effect of CarniQgel (ubiquinol and carnitine) on cytokines in patients with heart failure in the Tishcon study.Acta Cardiol 2007; 62: 349–354.
[76]Masaru K, Yu Y, Satomi K, & Kazumasa OM. Beneficial effect of coenzyme Q10 on increased oxidative and nitrative stress and inflammation and individual metabolic components developing in a rat model of metabolic syndrome. J Pharmacol Sci 2008; 107: 128–137.
[77]Tiano T, Belardinelli R, Carnevali P, Principi F, Seddau G, & Littarru GP. Effect of Coenzyme Q10 administration on endothelial function and extracellular superoxide dismutase in patients with ischemic heart disease. A double blind randomized controlled study. In process of being published in European Heart Journal 2007 Sep;28: 2249-55
[78]Fukai T, Folz RJ, Landmesser U, & Harrison GD. Extracellular superoxide dismutase and cardiovascular disease. Cardiovascular Research 2002; 55:239–249.
[79]Belardinelli R, Mucaj A, Lacalaprice F, Solenghi M, Seddaiu G, Principi F, Tiano L, & Littarru GP. Coenzyme Q10 and exercise training in chronic heart failure.European Heart Journal 2006; 27: 2675–2681.
[80]Atar D, Mortensen SA, Flachs H, Herzog WR. Coenzyme Q10 protects ischemic myocardium in an open-chest swine model. Clinical Investigator 1993; 71: 103–111.
[81]Nayler WG. The use of coenzyme Q10 to protect ischaemic heart muscle. in Yamamura Y, Folkers K, Ito (eds.): Biomedical and clinical Aspects of Coenzyme Q10, Vol. 2, Amsterdam, Elsevier, 1980, pp409–25
[82]Kwong LK, Kamzalov S, Rebrin I, Bayne AC, Jana CK, Morris P, Forster MJ & Sohal RS. Effects of coenzyme Q10 administration on its tissue concentrations, mitochondrial oxidant generation, and oxidative stress in the rat. Free Radical Biology & Medicine 2002; 33:627–638.
[83]Sohal RS, Kamzalov S, Sumien N, Ferguson M, Rebrin I, Heinrich KR, & Forster MJ. Effect of coenzyme Q10 intake on endogenous coenzyme Q content, mitochondrial electron transport chain, antioxidative defenses, and life span of mice. Free Radical Biology & Medicine 2006; 40: 480–487.
[84]Rosenfeldt FL, Pepe S, Ou R, Mariani JA, Rowland MA, Nagley P, & Ninnane AW. Coenzyme Q10 improves the tolerance of the senescent myocardium to aerobic and ischemic stress: studies in rats and in human atrial tissue. BioFactors 1999; 9: 291–299.
[85]Rosenfeldt FL, Marasco S, Lyon W, Wowk M, Sheeran F, Bailey M, Esmore D, Davis B, Pick A, Rabinov M, Smith J, Nagley P, & Pepe S. Coenzyme Q10 therapy before cardiac surgery improves mitochondrial function and in vivo contractility of myocardial tissue. Journal of Thoracic and Cardiovascular Surgery 2005; 129: 25–32.
[86]Redalieu E, Nilsson IM, Farley TM, Folkers K, & Koniuszy FR. Determination and levels of coenzyme Q10 in human blood. Anal Biochem 1968; 23: 132–140.
[87]Yalcin A, Kilinc E, Sagcan A, Kultursay H. Coenzyme Q10 concentrations in coronary disease Clin Biochem 2004; 37: 706–709.
[88]Hughes K, Lee BL, Feng X, Lee J, Ong CN. Coenzyme Q10 and differences in coronary heart disease risk in Asian Indians and Chinese Free Radic Biol Med 2002 Jan 15;32: 132-8.
[89]Folkers, K., Littarru, G. P., Ho, L., Runge, T. M., Havanonda, S., & Cooley, D. Evidence for a deficiency of coenzyme Q10 in human heart disease. Int J Vitam Nutr Res 1970; 40: 380–390.
[90]Langsjoen PH. A six-year clinical study of therapy of cardiomyopathy with coenzyme Q10. Int J Tissue React 1990; 12: 169–171.
[91]Littarru GP, Ho L, & Folkers K. Deficiency of coenzyme Q10 in human heart disease. Part I. Int J Vitam Nutr Res 1972; 42: 291–305.
[92]Littarru GP, Nakamura R, Ho L, Folkers K, Kuzell WC (October 1971). "Deficiency of Coenzyme Q10 in Gingival Tissue from Patients with Periodontal Disease". Proc. Natl. Acad. Sci. U.S.A. 1971; 68: 2332–5.
[93]Littarru GP, Ho L, Folkers K. Deficiency of coenzyme Q 10 in human heart disease II. Int J Vitam Nutr Res 1972; 42: 413–434.
[94]Sarter B. Coenzyme Q10 and cardiovascular disease: a review J Cardiovasc Nurs 2002; 16: 9–20.
[95]Langsjoen HA, Langsjoen PH, Langsjoen PH, Willis R, Folkers K. Usefulness of coenzyme Q10 in clinical cardiology: a long-term study Mol Aspects Med 1994; 15S: S165-175.
[96]Littarru GP, Tiano L Clinical aspects of coenzyme Q10: an update Curr Opin Clin Nutr Metab Care 2005; 8: 641–646.
[97]Kendler BS. Supplemental conditionally essential nutrients in cardiovascular disease therapy Cardiovasc Nurs 2006; 21: 9–16.
[98]Pepe S, Marasco SF, Hass SJ, Sheeran FL, Krum H, Rosenfeldt FL. Coenzyme Q10 in cardiovascular disease Mitochondrion 2007; 7S: S154–S167.
[99]Littarru GP, Tiano L. Clinical aspects of coenzyme Q10: an update Nutrition 2010; 26: 250–254.
[100]Hiasa Y, Ishida T, Maeda T, Iwanc K, Aihara T, Mori H. (1984). In K. Folkers & Y. Yamamura Y( Eds.), Effects of coenzyme Q10 in patients with stable angina pectoris. Biomedical and Clinical Aspects of Coenzyme Q Vol. 4. (pp.291-301) Amsterdam, Elsevier Science.
[101]Kamikawa T, Kobayashi A, Yamashita T, Hayashi H, Yamazaki N. Effects of coenzyme Q10 on exercise tolerance in chronic stable angina pectoris Am J Cardiol 1985; 56:247–251.
[102]Mazzola C, Guffanti EE, Vaccarella A, Meregalli M, Colnago R, Ferrario N. Non-invasive assessment of coenzyme Q10 in patients with chronic stable effort angina and moderate heart failure Curr Ther Res 1987; 41:923–932.
[103]Wilson MF, Frishman WH, Giles T, Sethi G, Greenberg SM, Brackett DJ. Coenzyme Q10 therapy and exercise duration in stable angina , in: Folkers K, Littarru GP, Yamagami T (Eds.), Biomedical and clinical aspects of coenzyme Q Elsevier, Amsterdam 1991; Vol.6: 339–348.
[104]Singh RB, Niaz MA, Sharma JP, Kumar R, Bishnoi I, Begom R. Plasma levels of antioxidant vitamins and oxidative stress in patients with acute myocardial infarction Acta Cardiol 1994; 49: 441–452
[105]Singh RB, Wander GS, Rastogi A, Shukla PK, Mittal A, Sharma JP, et al. Randomized, double-blind placebo-controlled trial of coenzyme Q10 in patients with acute myocardial infarction Cardiovasc Drugs Ther 1998; 12: 347–353.
[106]Permanetter B, Rössy W, Klein G, Weingartner F, Seidl KF, Blömer H. Ubiquinone (coenzyme Q10) in the long-term treatment of idiopathic dilated cardiomyopathy Eur Heart J 1992; 13: 1528–1533
[107]Hofman-Bang C, Rehnqvist N, Swedberg K, Wiklund I, Aström H. Coenzyme Q10 as an adjunctive in the treatment of chronic congestive heart failure The Q10 Study Group. J Card Fail 1995; 1: 101–7.
[108]Khatta M, Alexander BS, Krichten CM, Fisher ML, Freudenberger R,Robinson SW, et al. The effect of coenzyme Q10 in patients with congestive heart failure. Ann Intern Med 2000; 132: 636–40.
[109]Folkers K, Vadhanavikit S & Mortensen SA. Biochemical rationale and myocardial tissue data on the effective therapy of cardiomyopathy with coenzyme Q10. Proc Natl Acad Sci 1985; 2: 901–904.
[110]Langsjoen, P. 5th Annual International CoQ10 Symposium. 2007, November 9–12.Kobe,Japan
[111]Hosoe K, Kitano M, Kishida H, Kubo H, Fujii K, & Kitahara M. Study on safety and bioavailability of ubiquinol after single and 4-week multiple oral administration to healthy volunteers. Regul Toxicol Pharmacol 2007; 7: 19–28.
[112]Hathcock JN, & Shao A. Risk assessment for coenzyme Q10 (ubiquinone). Regul Toxicol Pharmacol 2006; 45: 282–288.
[113]Schardt F, Welzel D, Schiess W & Toda K. (1986) In K. Folkers & Y. Yamamura (Eds.), Effect of coenzyme Q10 on ischemia-induced ST-segment depression: a double-blind, placebo-controlled crossover study Biomedical and Clinical Aspects of Coenzyme Q Vol.5. (pp. 358–394) Amsterdam: Elsevier Science Publishers BV.
[114]Kumar A, Kaur H & Mohan V. Adjunctive Coenzyme Q10 Therapy in 106 Cases of Acute Coronary Syndrome (ACS). 2005 Fourth Conference of the International Coenzyme Q10 Association, LA, USA.
[115]Kumar A, Kaur H, & Mohan V. Atorvastatin alone/in combination with coenzyme Q10 in 103 cases of ischemic dilated cardiomyopathy. (2005) Fourth Conference of the International Coenzyme Q10 Association, LA, USA.
[116]Belardinelli R, Tiano L & Littarru GP. (2008). Oxidative stress, endothelial function and coenzyme Q10. BioFactors 32(1–4), 129–133.
[117]Stoker R, Bowry VW & Frei B. Ubiquinol-10 protects human low density lipoprotein more efficiently against lipid peroxidation than does α-tocopherol. Proc Natl Acad Sci 1991; 88: 1646–1650.
[118]Crane FL. Biochemical functions of coenzyme Q10. J Am Coll Nutr 2001; 20, 591–598.
[119]Tsuneki H, Sekizaki N, Suzuki T, Kobayashi S, Wada T, Okamoto T. et al. Coenzyme Q10 prevents high glucose-induced oxidative stress in human umbilical vein endothelial cells. Eur J Pharmacol 2007; 566(1–3): 1–10.
[120]Willis RA, Folkers K, Tucker JL, Ye CQ, Xia LJ, Tamagawa H. Lovastatin decreases coenzyme Q levels in rats. Proc Natl Acad Sci U S A. 1990; 87: 8928-30.
[121]Low P, Andersson M, Edlund C, Dallner G. Effects of mevinolin treatment on tissue dolichol and ubiquinone levels in the rat. Biochim Biophys Acta 1992 Nov 11; 1165: 102-9.
[122]Caliskan S, Caliskan M, Kuralay F, Onvural B. Effect of simvastatin therapy on blood and tissue ATP levels and erythrocyte membrane lipid composition. Res Exp Med 2000;199: 189-194.
[123]Satoh K, Yamato A, Nakai T, Hoshi K, Ichihara K. Effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on mitochondrial respiration in ischaemic dog hearts. Br J Pharmacol 1995 Sep; 116:1894-8.
[124]Morand OH, Aebi JD, Dehmlow H, Ji YH, Gains N, Lengsfeld H, Himber J.F. Ro 48-8.071,a new 2,3-oxidosqualene: lanosterolcyclase inhibitor lowering plasma cholesterol in hamsters, squirrel monkeys, and minipigs: comparison to simvastatin. J Lipid Res 1997 Feb; 38: 373-90.
[125]Diebold BA, Bhagavan NV, Guillory RJ. Influences of lovastatin administration on therespiratory burst of leukocytes and the phosphorylation potential of mitochondria in guinea pigs.Biochim Biophys Acta 1994 Jul 6;1200: 100-8.
[126]Ichihara K, Satoh K, Yamamoto A, Hoshi K. [Are all HMG-CoA reductase inhibitorsprotective against ischemic heart disease?] [Article in Japanese] Nippon Yakurigaku Zasshi 1999 Oct;114 Suppl 1:142P-l49P
[127]Watts GF, Castelluccio C, Rice-Evans C, Taub NA, Baum H, Quinn PJ. Plasma coenzymeQ (ubiquinone) concentrations in patients treated with simvastatin. J Clin Patho1 1993 Nov;46: 1055-7
[128]Ghirlanda G, Oradei A, Manto A, Lippa S, Uccioli L, Caputo S, Greco AV, Littarru GP. Evidence of plasma CoQ 10-lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled study. J Clin Pharmacol 1993 Mar;33: 226-9
[129]Folkers K, Langsjoen P, Willis R, Richardson P, Xia LJ, Ye CQ, Tamagawa H. Lovastatin decreases coenzyme Q levels in humans. Proc Natl Acad Sci USA 1990 Nov; 87: 8931-4.
[130]Bargossi AM, Battino M, Gaddi A, Fiorella PLY Grossi G, Barozzi G, Di Giulio R, Descovich G, Sassi S, Genova ML, et al. Exogenous CoQlo preserves plasma ubiquinone levels in patients treated with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Int J Clin Lab Res 1994; 24: 171-6.
[131]De Pinieux G, Chariot P, Ammi-Said M, Louarn F, Lejonc JL, Astier A, Jacotot B, Gherardi R. Lipid-lowering drugs and mitochondrial function: effects of HMG-CoA reductase inhibitors on serum ubiquinone and blood lactate/pyruvate ratio. Br J Clin Pharmacol 1996 Sep; 42: 333-7.
[132]Palomaki A, Malminiemi K, Metsa-Ketela T. Enhanced oxidizability of ubiquinol and alpha-tocopherol during lovastatin treatment. FEBS Lett. 1997 Jun 30; 410: 254-258.
[133]Mortensen SA, Leth A, Agner E, Rohde M. Dose-related decrease of serum coenzyme Q10 during treatment with HMG-CoA reductase inhibitors. Mol Aspects Med 1997; 18 Supp1: S137-44.
[134]Laaksonen R, Jokelainen K, Sahi T, Tikkanen MJ, Himberg JJ. Decreases in serum ubiquinone concentrations do not result in reduced levels in muscle tissue during short-term simvastatin treatment in humans. Clin Pharmacol Ther 1995 Jan; 57: 62-6.
[135]Bleske BE, Willis RA, Anthony M, Casselberry N, Datwani M, Uhley VE, Secontine SG, Shea MJ. The effect of pravastatin and atorvastatin on coenzyme Q10. Am Heart J 2001 Aug; 142: E2.
[136]Kitamura N, Yamaguchi A, Masami O, Sawatani O, Minoji T, Tamura H, Atobe M. Myocardial tissue level of coenzyme Q10 in patients with cardiac failure. In: Folkers K, Yamamura Y, (Eds) Biomedical and Clinical Aspects of Coenzyme Q. Elsevier, Amsterdam 1984; 4: 243-252.
[137]Folkers K, Vadhanavikit S, Mortensen SA. Biochemical rationale and myocardial tissue data on the effective therapy of cardiomyopathy with coenzyme Q10. Proc Natl Acad Sci USA 1985 Feb; 82:3,901-4.
[138]Kalen A, Appelkvist EL, Dallner G. Age-related changes in the lipid compositions of rat and human tissues. Lipids 1989 Ju1; 24:579-84.
[139]Soderberg M, Edlund C, Kristensson K, Dallner G. Lipid composition of different regions of the human brain during aging. J. Neurochem 1990; 54: 415-423.
[140]Pepe S, Lyon W, Marasco S, Wowk My Sheeran F, Ou R, Smith JA, Pick A, Rabinov M, Davis BB, Esmore DS , Rosenfeldt FL. A randomised, double-blind placebo controlled trial of preoperative coenzyme Q10 therapy: Improved outcomes in coronary artery bypass surgery. Circulation 2001; 104 (Suppl 11): 521 (abstract).
[141]Folkers K, Littarru GP, Ho L, Runge TM, Havanonda S, Cooley D. Evidence for adeficiency of coenzyme Q10 in human heart disease. Int Z Vitaminforsch 1970; 40: 380-90.
[142]Wong B, Lumma WC, Smith AM, Sisko JT, Wright SD, Cai TQ. Statins suppress THP-1 cell migration and secretion of matrix metalloproteinase 9 by inhibiting geranylgeranylation. J Leukoc Biol 2001 Jun; 69: 959-62.
[143]Alleva R, Tomasetti My Bompadre S, Littarru GP. Oxidation of LDL and their subfractions: kinetic aspects and CoQ10 content. Molec Aspects Med 1997; 18 Suppl: S105-S112.


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