Diabetes and vascular disease: Pathophysiology, clinical consequences, and medical therapy: Part i

European Heart Journal

Volumn 34, Issue 31, 2013, Pages 2436-2446

  Paneni, Francesco ^a,b   Beckman, Joshua A ^c   Creager, Mark A ^c   Cosentino, Francesco ^a,d  

^a UNIVERSITY OF ZURICH   (Switzerland)

^b IRCCS NEUROMED   (Italy)

^c HARVARD MEDICAL SCHOOL   (United States)

^d SAPIENZA UNIVERSITY OF ROME   (Italy)

Author keywords

Diabetes; Pathophysiology; Vascular disease

Indexed keywords

ADVANCED GLYCATION END PRODUCT; CYTOCHROME C; FIBRIN; FIBRINOGEN; FRUCTOSE 6 PHOSPHATE; GLIPIZIDE; HEXOSAMINE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INSULIN RECEPTOR SUBSTRATE 1; INSULIN RECEPTOR SUBSTRATE 2; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 1; INTERLEUKIN 6; METFORMIN; MICRORNA; MICRORNA 126; MICRORNA 222; MONOCYTE CHEMOTACTIC PROTEIN 1; NITRIC OXIDE; PEROXYNITRITE; PLASMINOGEN ACTIVATOR INHIBITOR 1; PROTEIN KINASE C; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; TUMOR NECROSIS FACTOR ALPHA; VASCULAR CELL ADHESION MOLECULE 1; VON WILLEBRAND FACTOR;

ANGIOGENESIS; APOPTOSIS; CARDIOVASCULAR DISEASE; CARDIOVASCULAR MORTALITY; CELL CYCLE PROGRESSION; CELL GROWTH; CORONARY ARTERY THROMBOSIS; DIABETES MELLITUS; ENDOTHELIAL DYSFUNCTION; ENDOTHELIAL PROGENITOR CELL; ENDOTHELIUM CELL; EPIGENETICS; GLYCEMIC CONTROL; HUMAN; HYPERGLYCEMIA; HYPERINSULINEMIA; INSULIN RESISTANCE; MACROPHAGE ACTIVATION; NITROSYLATION; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; OXIDATIVE STRESS; PATHOPHYSIOLOGY; PHOSPHOLIPID MEMBRANE; PLATELET REACTIVITY; PRIORITY JOURNAL; PROTEIN EXPRESSION; REDOX STRESS; REVIEW; THROMBOSIS; UPREGULATION; VASCULAR DISEASE; VASCULAR ENDOTHELIUM; VASCULARIZATION;

DIABETES; PATHOPHYSIOLOGY; VASCULAR DISEASE;

ANIMALS; ATHEROSCLEROSIS; DIABETES MELLITUS, TYPE 2; DIABETIC ANGIOPATHIES; ENDOTHELIUM, VASCULAR; HUMANS; HYPERGLYCEMIA; INSULIN RESISTANCE; MICE; MICRORNAS; NITRIC OXIDE; OBESITY; OXIDATIVE STRESS; PLATELET AGGREGATION; REACTIVE OXYGEN SPECIES; THROMBOSIS;

EID: 84882336972     PISSN: 0195668X     EISSN: 15229645     Source Type: Journal    
DOI: 10.1093/eurheartj/eht149     Document Type: Review

References (102)

1. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004;27: 1047-1053.
2. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 2003;26(Suppl 1):S5-S20
3. DeFronzo RA, Ferrannini E. Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 1991;14:173-194.
4. Naudi A, Jove M, Ayala V, Cassanye A, Serrano J, Gonzalo H, Boada J, Prat J, Portero-Otin M, Pamplona R. Cellular dysfunction in diabetes as maladaptive response to mitochondrial oxidative stress. Exp Diabetes Res 2012;2012:696215.
5. WeiM, Gaskill SP, Haffner SM, SternMP. Effects of diabetes and level of glycemia on all-cause and cardiovascular mortality. The San Antonio Heart Study. Diabetes Care 1998;21:1167-1172.
6. Coutinho M, Gerstein HC,Wang Y, Yusuf S. The relationship between glucose and incident cardiovascular events.Ametaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years. Diabetes Care 1999;22: 233-240.
7. Rutter MK, NestoRW. Blood pressure, lipids and glucose in type 2 diabetes: How low should we go Re-discovering personalized care. Eur Heart J 2011;32: 2247-2255.
8. Bartnik M, Cosentino F. Dysglycaemia, cardiovascular outcome and treatment. Is the jury still out Eur Heart J 2009;30:1301-1304.
9. Creager MA, Luscher TF, Cosentino F, Beckman JA. Diabetes and vascular disease: Pathophysiology, clinical consequences, and medical therapy: Part I. Circulation 2003;108:1527-1532.
10. Hink U, Li H, Mollnau H, Oelze M, Matheis E, Hartmann M, Skatchkov M, Thaiss F, Stahl RA, Warnholtz A, Meinertz T, Griendling K, Harrison DG, Forstermann U, Munzel T. Mechanisms underlying endothelial dysfunction in diabetes mellitus. Circ Res 2001;88:E14-E22.
11. Lerman A, Zeiher AM. Endothelial function: cardiac events. Circulation 2005;111: 363-368.
12. Nishikawa T, Edelstein D, Du XL, Yamagishi S, Matsumura T, Kaneda Y, Yorek MA, Beebe D, Oates PJ, Hammes HP, Giardino I, Brownlee M. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 2000;404:787-790.
13. Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res 2010; 107:1058-1070.
14. Geraldes P, King GL. Activation of protein kinase C isoforms and its impact on diabetic complications. Circ Res 2010;106:1319-1331.
15. Inoguchi T, Li P, Umeda F, Yu HY, Kakimoto M, Imamura M, Aoki T, Etoh T, Hashimoto T, Naruse M, Sano H, Utsumi H, Nawata H. High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C-dependent activation of NAD(P)Hoxidase in cultured vascular cells. Diabetes 2000;49:1939-1945.
16. Quagliaro L, Piconi L, Assaloni R, Martinelli L, Motz E, Ceriello A. Intermittent high glucose enhances apoptosis related to oxidative stress in human umbilical vein endothelial cells: the role of protein kinase c and NAD(P)H-oxidase activation. Diabetes 2003;52:2795-2804.
17. Cosentino F, Francia P, Camici GG, Pelicci PG, Luscher TF, Volpe M. Final common molecular pathways of aging and cardiovascular disease: role of the p66shc protein. Arterioscler Thromb Vasc Biol 2008;28:622-628.
18. Paneni F, Mocharla P, Akhmedov A, Costantino S, Osto E, Volpe M, Luscher TF, Cosentino F. Gene silencing of the mitochondrial adaptor p66shc suppresses vascular hyperglycemic memory in diabetes. Circ Res 2012;111:278-89.
19. Camici GG, Schiavoni M, Francia P, Bachschmid M, Martin-Padura I, Hersberger M, Tanner FC, PelicciP, Volpe M, Anversa P, Luscher TF, Cosentino F. Genetic deletion of p66(shc) adaptor protein prevents hyperglycemia-induced endothelial dysfunction and oxidative stress. Proc Natl Acad Sci USA 2007;104:5217-5222.
20. Pagnin E, Fadini G, de Toni R, Tiengo A, Calo L,Avogaro A. Diabetes induces p66shc gene expression in human peripheral blood mononuclear cells: relationship to oxidative stress. J Clin Endocrinol Metab 2005;90:1130-1136.
21. Tomilov AA, Bicocca V, Schoenfeld RA, Giorgio M, Migliaccio E, Ramsey JJ, Hagopian K, Pelicci PG, Cortopassi GA. Decreased superoxide production in macrophages of long-lived p66shc knock-out mice. J Biol Chem 2010;285: 1153-1165.
22. Shi Y, Cosentino F, Camici GG, Akhmedov A, Vanhoutte PM, Tanner FC, Luscher TF. Oxidized low-density lipoprotein activates p66shc via lectin-like oxidized low-density lipoprotein receptor-1, protein kinase c-beta, and c-jun n-terminal kinase kinase in human endothelial cells. Arterioscler Thromb Vasc Biol 2011;31:2090-2097.
23. Cosentino F, Hishikawa K, Katusic ZS, Luscher TF. High glucose increases nitric oxide synthase expression and superoxide anion generation in human aortic endothelial cells. Circulation 1997;96:25-28.
24. Alp NJ, Channon KM. Regulation of endothelial nitric oxide synthase by tetrahydrobiopterin in vascular disease. Arterioscler Thromb Vasc Biol 2004;24:413-420.
25. Du XL, Edelstein D, Dimmeler S, Ju Q, Sui C, Brownlee M. Hyperglycemia inhibits endothelial nitric oxide synthase activity by posttranslational modification at the akt site. J Clin Invest 2001;108:1341-1348.
26. Cardillo C, Campia U, Bryant MB, Panza JA. Increased activity of endogenous endothelin in patients with type II diabetes mellitus. Circulation 2002;106: 1783-1787.
27. Kouroedov A, Eto M, Joch H, Volpe M, Luscher TF, Cosentino F. Selective inhibition of protein kinase cbeta2 prevents acute effects of high glucose on vascular cell adhesion molecule-1 expression in human endothelial cells. Circulation 2004;110: 91-96.
28. Cosentino F, Eto M, De Paolis P, van der Loo B, Bachschmid M, Ullrich V, KouroedovA, Delli Gatti C, Joch H, Volpe M, Luscher TF. High glucose causes upregulation of cyclooxygenase-2 and alters prostanoid profile in human endothelial cells: role of protein kinase C and reactive oxygen species. Circulation 2003;107: 1017-1023.
29. Brouwers O, Niessen PM, Haenen G, Miyata T, Brownlee M, Stehouwer CD, De Mey JG, Schalkwijk CG. Hyperglycaemia-induced impairment of endotheliumdependent vasorelaxation in rat mesenteric arteries is mediated by intracellular methylglyoxal levels in a pathway dependent on oxidative stress. Diabetologia 2010;53:989-1000.
30. Yan SF, Ramasamy R, Schmidt AM. The rage axis: a fundamental mechanism signaling danger to the vulnerable vasculature. Circ Res 2010;106:842-853.
31. Sena CM, Matafome P, Crisostomo J, Rodrigues L, Fernandes R, Pereira P, Seica RM. Methylglyoxal promotes oxidative stress and endothelial dysfunction. Pharmacol Res 2012;65:497-506.
32. Bierhaus A, Humpert PM, Morcos M,Wendt T, Chavakis T, Arnold B, Stern DM, Nawroth PP. Understanding rage, the receptor for advanced glycation end products. J Mol Med (Berl) 2005;83:876-886.
33. Fulop N, Marchase RB, Chatham JC. Role of protein o-linked n-acetyl-glucosamine in mediating cell function and survival in the cardiovascular system. Cardiovasc Res 2007;73:288-297.
34. Buse MG. Hexosamines, insulin resistance, and the complications of diabetes: current status. Am J Physiol Endocrinol Metab 2006;290:E1-E8.
35. Lee AY, Chung SS. Contributions of polyol pathway to oxidative stress in diabetic cataract. FASEB J 1999;13:23-30.
36. Vikramadithyan RK, Hu Y, Noh HL, Liang CP, Hallam K, Tall AR, Ramasamy R, Goldberg IJ. Human aldose reductase expression accelerates diabetic atherosclerosis in transgenic mice. J Clin Invest 2005;115:2434-2443.
37. Saltiel AR, Kahn CR. Insulin signalling and the regulation of glucose and lipid metabolism. Nature 2001;414:799-806.
38. Bhatia LS, Curzen NP, Calder PC, Byrne CD. Non-alcoholic fatty liver disease: a new and important cardiovascular risk factor Eur Heart J 2012;33:1190-1200.
39. Hossain P, Kawar B, El Nahas M. Obesity and diabetes in the developing world-a growing challenge. N Engl J Med 2007;356:213-215.
40. Shulman GI. Cellular mechanisms of insulin resistance. J Clin Invest 2000;106: 171-176.
41. Cavelti-Weder C, Babians-Brunner A, Keller C, Stahel MA, Kurz-Levin M, Zayed H, Solinger AM, Mandrup-Poulsen T, Dinarello CA, Donath MY. Effects of gevokizumab on glycemia and inflammatory markers in type 2 diabetes. Diabetes Care 2012; 35:1654-1662.
42. Kim JA, Montagnani M, Koh KK, Quon MJ. Reciprocal relationships between insulin resistance and endothelial dysfunction: molecular and pathophysiological mechanisms. Circulation 2006;113:1888-1904.
43. Kim JK. Endothelial nuclear factor kappab in obesity and aging: is endothelial nuclear factor kappaB amaster regulator of inflammation and insulin resistance Circulation 2012;125:1081-1083.
44. Du X, Edelstein D, Obici S, Higham N, Zou MH, Brownlee M. Insulin resistance reduces arterial prostacyclin synthase andeNOsactivities by increasing endothelial fatty acid oxidation. J Clin Invest 2006;116:1071-1080.
45. Rask-Madsen C, Li Q, Freund B, Feather D, Abramov R, Wu IH, Chen K, Yamamoto-Hiraoka J, Goldenbogen J, Sotiropoulos KB, Clermont A, Geraldes P, Dall'Osso C,Wagers AJ, Huang PL, Rekhter M, Scalia R, Kahn CR, King GL. Loss of insulin signaling in vascular endothelial cells accelerates atherosclerosis in apolipoprotein e null mice. Cell Metab 2010;11:379-389.
46. Olefsky JM, Glass CK. Macrophages, inflammation, and insulin resistance. Annu Rev Physiol 2010;72:219-246.
47. Gray S, Kim JK.Newinsights into insulin resistance in the diabetic heart. Trends Endocrinol Metab 2011;22:394-403.
48. HasegawaY, Saito T, OgiharaT, Ishigaki Y, Yamada T, Imai J, Uno K, Gao J, Kaneko K, Shimosawa T, Asano T, Fujita T, Oka Y, Katagiri H. Blockade of the nuclear factorkappab pathway in the endothelium prevents insulin resistance and prolongs life spans. Circulation 2012;125:1122-1133.
49. KubotaT,KubotaN,KumagaiH,Yamaguchi S,KozonoH,TakahashiT, InoueM, Itoh S, Takamoto I, Sasako T, Kumagai K, Kawai T, Hashimoto S, Kobayashi T, Sato M, Tokuyama K, Nishimura S, Tsunoda M, Ide T, Murakami K, Yamazaki T, Ezaki O, Kawamura K, Masuda H, Moroi M, Sugi K, Oike Y, Shimokawa H, Yanagihara N, Tsutsui M, Terauchi Y, Tobe K, Nagai R, Kamata K, Inoue K, Kodama T, Ueki K, Kadowaki T. Impaired insulin signaling in endothelial cells reduces insulin-induced glucose uptake by skeletal muscle. Cell Metab 2011;13:294-307.
50. Vitale C, Mercuro G, Cornoldi A, Fini M, Volterrani M, Rosano GM. Metformin improves endothelial function in patients with metabolic syndrome. J Intern Med 2005;258:250-256.
51. Naka KK, Papathanassiou K, Bechlioulis A, Pappas K, Kazakos N, Kanioglou C, Papafaklis MI, Kostoula A, Vezyraki P, Makriyiannis D, Tsatsoulis A, Michalis LK. Rosiglitazone improves endothelial function in patients with type 2 diabetes treated with insulin. Diab Vasc Dis Res 2011;8:195-201.
52. Wang TD, Chen WJ, Cheng WC, Lin JW, Chen MF, Lee YT. Relation of improvement in endothelium-dependent flow-mediated vasodilation after rosiglitazone to changes in asymmetric dimethylarginine, endothelin-1, and C-reactive protein in nondiabetic patients with the metabolic syndrome. Am J Cardiol 2006;98: 1057-1062.
53. Zhang H, Dellsperger KC, Zhang C. The link between metabolic abnormalities and endothelial dysfunction in type 2 diabetes: an update. Basic Res Cardiol 2012;107: 237
54. Lee M, Saver JL, Towfighi A, Chow J, Ovbiagele B. Efficacy of fibrates for cardiovascular risk reduction in persons with atherogenic dyslipidemia: a meta-analysis. Atherosclerosis 2011;217:492-498.
55. Fruchart JC, Sacks F, Hermans MP, Assmann G, BrownWV, Ceska R, Chapman MJ, Dodson PM, Fioretto P, Ginsberg HN, KadowakiT, Lablanche JM, Marx N, Plutzky J, Reiner Z, Rosenson RS, Staels B, Stock JK, Sy R,Wanner C, Zambon A, Zimmet P. The residual risk reduction initiative: a call to action to reduce residual vascular risk in patients with dyslipidemia. Am J Cardiol 2008;102:1K-34K.
56. Arca M, Montali A, Valiante S, Campagna F, Pigna G, Paoletti V, Antonini R, Barilla F, Tanzilli G, Vestri A, Gaudio C. Usefulness of atherogenic dyslipidemia for predicting cardiovascular risk in patients with angiographically defined coronary artery disease. Am J Cardiol 2007;100:1511-1516.
57. Chaudhuri A, Janicke D, WilsonMF, Tripathy D, Garg R, Bandyopadhyay A, Calieri J, Hoffmeyer D, Syed T, Ghanim H, Aljada A, Dandona P. Anti-inflammatory and profibrinolytic effect of insulin in acute ST-segment-elevation myocardial infarction. Circulation 2004;109:849-854.
58. Vinik AI, Erbas T, Park TS, Nolan R, Pittenger GL. Platelet dysfunction in type 2 diabetes. Diabetes Care 2001;24:1476-1485.
59. Ferreira IA, Mocking AI, Feijge MA, Gorter G, van Haeften TW, Heemskerk JW, Akkerman JW. Platelet inhibition by insulin is absent in type 2 diabetes mellitus. Arterioscler Thromb Vasc Biol 2006;26:417-422.
60. Basili S, Pacini G, Guagnano MT, Manigrasso MR, Santilli F, Pettinella C, Ciabattoni G, Patrono C, Davi G. Insulin resistance as a determinant of platelet activation in obese women. J Am Coll Cardiol 2006;48:2531-2538.
61. Rocca B, Santilli F, Pitocco D, Mucci L, Petrucci G, Vitacolonna E, Lattanzio S, Mattoscio D, Zaccardi F, Liani R, Vazzana N, Del Ponte A, Ferrante E, Martini F, Cardillo C, Morosetti R, Mirabella M, Ghirlanda G, Davi G, Patrono C. The recovery of platelet cyclooxygenase activity explains interindividual variability in responsiveness to low-dose aspirin in patients with and without diabetes. J Thromb Haemost 2012;10:1220-1230.
62. Sattar N,Wannamethee SG, Forouhi NG. Novel biochemical risk factors for type 2 diabetes: pathogenic insights or prediction possibilities Diabetologia 2008;51: 926-940.
63. Taube A, Schlich R, Sell H, Eckardt K, Eckel J. Inflammation and metabolic dysfunction: links to cardiovascular diseases. Am J Physiol Heart Circ Physiol 2012;302: H2148-H2165.
64. Li ZY,Wang P, Miao CY. Adipokines in inflammation, insulin resistance and cardiovascular disease. Clin Exp Pharmacol Physiol 2011;38:888-896.
65. Shantikumar S, Caporali A, Emanueli C. Role of microRNAs in diabetes and its cardiovascular complications. Cardiovasc Res 2012;93:583-593.
66. Zampetaki A, Mayr M. MicroRNAs in vascular and metabolic disease. Circ Res 2012; 110:508-522.
67. Zampetaki A, Kiechl S, Drozdov I, Willeit P, Mayr U, Prokopi M, Mayr A,Weger S, Oberhollenzer F, Bonora E, Shah A, Willeit J, Mayr M. Plasma microrna profiling reveals loss of endothelial mir-126 and other microRNAs in type 2 diabetes. Circ Res 2010;107:810-817.
68. Karolina DS, Armugam A, Tavintharan S,Wong MT, Lim SC, Sum CF, Jeyaseelan K. MicroRNA 144 impairs insulin signaling by inhibiting the expression of insulin receptor substrate 1 in type 2 diabetes mellitus. PLoS One 2011;6:e22839.
69. Dehwah MA, Xu A, Huang Q. MicroRNAs and type 2 diabetes/obesity. J Genet Genomics 2012;39:11-18.
70. Wang XH, Qian RZ, ZhangW, Chen SF, Jin HM, Hu RM. MicroRNA-320 expression in myocardial microvascular endothelial cells and its relationship with insulinlike growth factor-1 in type 2 diabetic rats. Clin Exp Pharmacol Physiol 2009;36: 181-188.
71. Li Y, Song YH, Li F, Yang T, Lu YW, Geng YJ. MicroRNA-221 regulates high glucose-induced endothelial dysfunction. Biochem Biophys Res Commun 2009;381: 81-83.
72. Togliatto G, Trombetta A, Dentelli P, Rosso A, Brizzi MF. Mir221/mir222-driven post-transcriptional regulation of p27kip1 and p57kip2 is crucial for high-glucoseand age-mediated vascular cell damage. Diabetologia 2011;54:1930-1940.
73. Caporali A, Meloni M, Vollenkle C, Bonci D, Sala-Newby GB, Addis R, Spinetti G, Losa S, Masson R, Baker AH, Agami R, le Sage C, Condorelli G, Madeddu P, Martelli F, Emanueli C. Deregulation of microRNA-503 contributes to diabetes mellitus-induced impairment of endothelial function and reparative angiogenesis after limb ischemia. Circulation 2011;123:282-291.
74. Meng S, Cao JT, Zhang B, Zhou Q, Shen CX, Wang CQ. Downregulation of microrna-126 in endothelial progenitor cells from diabetes patients, impairs their functional properties, via target gene SPRED-1. J Mol Cell Cardiol 2012;53:64-72.
75. Wang DE. MicroRNA regulation and its biological significance in personalized medicine and aging. Curr Genomics 2009;10:143.
76. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998;339:229-234.
77. Roffi M, Angiolillo DJ, Kappetein AP. Current concepts on coronary revascularization in diabetic patients. Eur Heart J 2011;32:2748-2757.
78. RadkePW, Schunkert H. Diabetics with acute coronary syndrome: advances, challenges, and uncertainties. Eur Heart J 2010;31:2971-2973.
79. Grant PJ. Diabetes mellitus as a prothrombotic condition. J Intern Med 2007;262: 157-172.
80. Vazzana N, Ranalli P, Cuccurullo C, Davi G. Diabetes mellitus and thrombosis. Thromb Res 2012;129:371-377.
81. Beckman JA, Creager MA, Libby P. Diabetes and atherosclerosis: epidemiology, pathophysiology, and management. JAMA 2002;287:2570-2581.
82. Lemkes BA, Hermanides J, Devries JH, Holleman F, Meijers JC, Hoekstra JB. Hyperglycemia: a prothrombotic factor J Thromb Haemost 2010;8:1663-1669.
83. Boden G, Rao AK. Effects of hyperglycemia and hyperinsulinemia on the tissue factor pathway of blood coagulation. Curr Diab Rep 2007;7:223-227.
84. Vaidyula VR, Rao AK, Mozzoli M, Homko C, Cheung P, Boden G. Effects of hyperglycemia and hyperinsulinemia on circulating tissue factor procoagulant activity and platelet CD40 ligand. Diabetes 2006;55:202-208.
85. Tsimerman G, Roguin A, Bachar A, Melamed E, Brenner B, Aharon A. Involvement of microparticles in diabetic vascular complications. Thromb Haemost 2011;106: 310-321.
86. Sinning JM, Losch J, Walenta K, Bohm M, Nickenig G, Werner N. Circulating cd31+/annexin v+ microparticles correlate with cardiovascular outcomes. Eur Heart J 2011;32:2034-2041.
87. Linden MD, Tran H,Woods R, Tonkin A. High platelet reactivity and antiplatelet therapy resistance. Semin Thromb Hemost 2012;38:200-212.
88. Boussageon R, Bejan-Angoulvant T, Saadatian-Elahi M, Lafont S, Bergeonneau C, Kassai B, Erpeldinger S, Wright JM, Gueyffier F, Cornu C. Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials. BMJ 2011;343:d4169.
89. Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, Marre M, Cooper M, Glasziou P, Grobbee D, Hamet P, Harrap S, Heller S, Liu L, Mancia G, Mogensen CE, Pan C, Poulter N, Rodgers A, Williams B, Bompoint S, de Galan BE, Joshi R, Travert F. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008;358:2560-2572.
90. Gerstein HC, Miller ME, Byington RP, GoffDCJr, Bigger JT, Buse JB, Cushman WC, Genuth S, Ismail-Beigi F, Grimm RH Jr, Probstfield JL, Simons-Morton DG, Friedewald WT. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008;358:2545-2559.
91. Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, Zieve FJ, Marks J, Davis SN, Hayward R, Warren SR, Goldman S, McCarren M, Vitek ME, Henderson WG, Huang GD. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 2009;360:129-139.
92. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329: 977-986.
93. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008;359:1577-1589.
94. Ihnat MA, Thorpe JE, Kamat CD, Szabo C, Green DE, Warnke LA, Lacza Z, Cselenyak A, Ross K, Shakir S, Piconi L, Kaltreider RC, Ceriello A. Reactive oxygen species mediate a cellular 'memory' of high glucose stress signalling. Diabetologia 2007;50:1523-1531.
95. Ceriello A, Esposito K, Ihnat M, Zhang J, Giugliano D. Simultaneous control of hyperglycemia and oxidative stress normalizes enhanced thrombin generation in type 1 diabetes. J Thromb Haemost 2009;7:1228-1230.
96. Ceriello A. Hypothesis: The 'metabolic memory', the new challenge of diabetes. Diabetes Res Clin Pract 2009;86(Suppl 1):S2-S6.
97. Keating ST, El-Osta A. Chromatin modifications associated with diabetes. J Cardiovasc Transl Res 2012;5:399-412.
98. El-Osta A, Brasacchio D, Yao D, Pocai A, Jones PL, Roeder RG, Cooper ME, Brownlee M. Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia. J Exp Med 2008;205: 2409-2417.
99. Zheng Z, Chen H, Li J, Li T, Zheng B, Zheng Y, Jin H, He Y, Gu Q, Xu X. Sirtuin 1- mediated cellular metabolicmemoryof high glucose via the lkb1/ampk/ros pathway and therapeutic effects of metformin. Diabetes 2012;61:217-228.
100. Schisano B, Tripathi G, McGee K, McTernan PG, Ceriello A. Glucose oscillations, more than constant high glucose, induce p53 activation and a metabolic memory in human endothelial cells. Diabetologia 2011;54:1219-1226.
101. Zhou S, Chen HZ,Wan YZ, Zhang QJ,Wei YS, Huang S, Liu JJ, Lu YB, Zhang ZQ, Yang RF, Zhang R, Cai H, Liu DP, Liang CC. Repression of p66shc expression by SIRT1 contributes to the prevention of hyperglycemia-induced endothelial dysfunction. Circ Res 2011;109:639-648.
102. Kim CS, Jung SB, Naqvi A, Hoffman TA, DeRicco J, Yamamori T, Cole MP, Jeon BH, Irani K. P53 impairs endothelium-dependent vasomotor function through transcriptional upregulation of p66shc. Circ Res 2008;103:1441-1450.