Statin therapy in acute coronary syndromes: Mechanistic insight into clinical benefit

Arteriosclerosis, Thrombosis, and Vascular Biology

Volumn 22, Issue 10, 2002, Pages 1524-1534

  Sposito, Andrei C ^a,b   Chapman, M John ^a  

^a PITIÉ SALPÊTRIÈRE HOSPITAL   (France)

^b UNIVERSITY OF SÃO PAULO   (Brazil)

Author keywords

Acute coronary syndromes; Secondary prevention; Statins

Indexed keywords

HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INTERMEDIATE DENSITY LIPOPROTEIN; LOW DENSITY LIPOPROTEIN; STATINE; VERY LOW DENSITY LIPOPROTEIN;

ANTIINFLAMMATORY ACTIVITY; BLOOD CLOT LYSIS; CORONARY ARTERY DISEASE; HEART MUSCLE ISCHEMIA; HUMAN; INFLAMMATION; LIPID STORAGE; PATIENT COMPLIANCE; PRIORITY JOURNAL; REPERFUSION INJURY; SHORT SURVEY; THROMBOGENESIS;

ACUTE DISEASE; ANIMALS; ANTICHOLESTEREMIC AGENTS; CORONARY ARTERIOSCLEROSIS; CORONARY DISEASE; HUMANS; INFLAMMATION; SYNDROME; THROMBOSIS;

EID: 0036790614     PISSN: 10795642     EISSN: None     Source Type: Journal    
DOI: 10.1161/01.ATV.0000032033.39301.6A     Document Type: Short Survey

References (138)

1. Waters DD, Hsue PY. What is the role of intensive cholesterol lowering in the treatment of acute coronary syndromes? Am J Cardiol. 2001;88:7-16.
2. Matsuda M, Korn BS, Hammer RE, Moon YA, Komuro R, Horton JD, Goldstein JL, Brown MS, Shimomura I. SREBP cleavage-activating protein (SCAP) is required for increased lipid synthesis in liver induced by cholesterol deprivation and insulin elevation. Genes Dev. 2001;15:1206-1216.
3. Correia LC, Sposito AC, Passos LC, Lima JC, Braga JC, Rocha MS, Esteves JP, D'Oliveira A. Short-term effect of atorvastatin (80 mg) on plasma lipids of patients with unstable angina pectoris or non-Q wave acute myocardial infarction. Am J Cardiol. 2002;90:162-164.
4. Jones P, Kafonek S, Laurora I, Hunninghake D. Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study). Am J Cardiol. 1998;81:582-587.
5. Davies MJ. Going from immutable to mutable atherosclerotic plaques. Am J Cardiol. 2001;88:2F-9F.
6. Davignon J, Laaksonen R. Low-density lipoprotein-independent effects of statins. Curr Opin Lipidol. 1999;10:543-559.
7. Chen L, Chester MR, Crook R, Kaski JC. Differential progression of complex culprit stenoses in patients with stable and unstable angina pectoris. J Am Coll Cardiol. 1996;28:597-603.
8. Buffon A, Biasucci LM, Liuzzo G, D'Onofrio G, Crea F, Maseri A. Widespread coronary inflammation in unstable angina. N Engl J Med. 2002;347:5-12.
9. Goldstein JA, Demetriou D, Grines CL, Pica M, Shoukfeh M, O'Neill WW. Multiple complex coronary plaques in patients with acute myocardial infarction. N Engl J Med. 2000;343:915-922.
10. Guazzi MD, Bussotti M, Grancini L, De Cesare N, Guazzi M, Pera IL, Loaldi A. Evidence of multifocal activity of coronary disease in patients with acute myocardial infarction. Circulation. 1997;96:1145-1151.
11. Asakura M, Ueda Y, Yamaguchi O, Adachi T, Hirayama A, Hori M, Kodama K. Extensive development of vulnerable plaques as a pan-coronary process in patients with myocardial infarction: an angioscopic study. J Am Coll Cardiol. 2001;37:1284-1288.
12. Falk E. Why do plaques rupture? Circulation. 1992;86(suppl III):III-30-III-42.
13. Libby P. What have we learned about the biology of atherosclerosis?: the role of inflammation. Am J Cardiol. 2001;88:3-6.
14. Hangartner JR, Charleston AJ, Davies MJ, Thomas AC. Morphological characteristics of clinically significant coronary artery stenosis in stable angina. Br Heart J. 1986;56:501-508.
15. Davies MJ, Thomas A. Thrombosis and acute coronary-artery lesions in sudden cardiac ischemic death. N Engl J Med. 1984;310:1137-1140.
16. Falk E. Unstable angina with fatal outcome: dynamic coronary thrombosis leading to infarction and/or sudden death: autopsy evidence of recurrent mural thrombosis with peripheral embolization culminating in total vascular occlusion. Circulation. 1985;71:699-708.
17. Mehta JL, Saldeen TG, Rand K. Interactive role of infection, inflammation and traditional risk factors in atherosclerosis and coronary artery disease. J Am Coll Cardiol. 1998;31:1217-1225.
18. Crisby M, Nordin-Fredriksson G, Shah PK, Yano J, Zhu J, Nilsson J. Pravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell death in human carotid plaques: implications for plaque stabilization. Circulation. 2001;103:926-933.
19. Aikawa M, Voglic SJ, Sugiyama S, Rabkin E, Taubman MB, Fallon JT, Libby P. Dietary lipid lowering reduces tissue factor expression in rabbit atheroma. Circulation. 1999;100:1215-1222.
20. Bustos C, Hernandez-Presa MA, Ortego M, Tunon J, Ortega L, Perez F, Diaz C, Hernandez G, Egido J. HMG-CoA reductase inhibition by atorvastatin reduces neointimal inflammation in a rabbit model of atherosclerosis. J Am Coll Cardiol. 1998;32:2057-2064.
21. Aikawa M, Rabkin E, Sugiyama S, Voglic SJ, Fukumoto Y, Furukawa Y, Shiomi M, Schoen FJ, Libby P. An HMG-CoA reductase inhibitor, cerivastatin, suppresses growth of macrophages expressing matrix metalloproteinases and tissue factor in vivo and in vitro. Circulation. 2001;103:276-283.
22. Aikawa M, Rabkin E, Voglic SJ, Shing H, Nagai R, Schoen FJ, Libby P. Lipid lowering promotes accumulation of mature smooth muscle cells expressing smooth muscle myosin heavy chain isoforms in rabbit atheroma. Circ Res. 1998;83:1015-1026.
23. Aikawa M, Rabkin E, Okada Y, Voglic SJ, Clinton SK, Brinckerhoff CE, Sukhova GK, Libby P. Lipid lowering by diet reduces matrix metalloproteinase activity and increases collagen content of rabbit atheroma: a potential mechanism of lesion stabilization. Circulation. 1998;97:2433-2444.
24. Bellosta S, Via D, Canavesi M, Pfister P, Fumagalli R, Paoletti R, Bernini F. HMG-CoA reductase inhibitors reduce MMP-9 secretion by macrophages. Arterioscler Thromb Vasc Biol. 1998;18:1671-1678.
25. Kurakata S, Kada M, Shimada Y, Komai T, Nomoto K. Effects of different inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, pravastatin sodium and simvastatin, on sterol synthesis and immunological functions in human lymphocytes in vitro. Immunopharmacology. 1996;34:51-61.
26. Kwak B, Mulhaupt F, Myit S, Mach F. Statins as a newly recognized type of immunomodulator. Nat Med. 2000;6:1399-1402.
27. Romano M, Diomede L, Sironi M, Massimiliano L, Sottocorno M, Polentarutti N, Guglielmotti A, Albani D, Bruno A, Fruscella P, Salmona M, Vecchi A, Pinza M, Mantovani A. Inhibition of monocyte chemotactic protein-1 synthesis by statins. Lab Invest. 2000;80:1095-1100.
28. Guijarro C, Blanco-Colio LM, Ortego M, Alonso C, Ortiz A, Plaza JJ, Diaz C, Hernandez G, Egido J. 3-Hydroxy-3-methylglutaryl coenzyme a reductase and isoprenylation inhibitors induce apoptosis of vascular smooth muscle cells in culture. Circ Res. 1998;83:490-500.
29. Alaei P, MacNulty EE, Ryder NS. Inhibition of protein prenylation down-regulates signalling by inflammatory mediators in human keratinocytes. Biochem Biophys Res Commun. 1996;222:133-138.
30. Ni W, Egashira K, Kataoka C, Kitamoto S, Koyanagi M, Inoue S, Takeshita A. Antiinflammatory and antiarteriosclerotic actions of HMG-CoA reductase inhibitors in a rat model of chronic inhibition of nitric oxide synthesis. Circ Res. 2001;89:415-421.
31. Laufs U, Endres M, Custodis F, Gertz K, Nickenig G, Liao JK, Bohm M. Suppression of endothelial nitric oxide production after withdrawal of statin treatment is mediated by negative feedback regulation of rho GTPase gene transcription. Circulation. 2000;102:3104-3110.
32. Weitz-Schmidt G, Welzenbach K, Brinkmann V, Kamata T, Kallen J, Bruns C, Cottens S, Takada Y, Hommel U. Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site. Nat Med. 2001;7:687-692.
33. Holm T, Andreassen AK, Ueland T, Kjekshus J, Froland SS, Kjekshus E, Simonsen S, Aukrust P, Gullestad L. Effect of pravastatin on plasma markers of inflammation and peripheral endothelial function in male heart transplant recipients. Am J Cardiol. 2001;87:815-818.
34. Holdaas H, Jardine AG, Wheeler DC, Brekke IB, Conlon PJ, Fellstrom B, Hammad A, Holme I, Isoniemi H, Moore R, Rowe PA, Sweny P, Talbot DA, Wadstrom J, Ostraat O. Effect of fluvastatin on acute renal allograft rejection: a randomized multicenter trial. Kidney Int. 2001;60:1990-1997.
35. Weis M, Pehlivanli S, Meiser BM, von Scheidt W. Simvastatin treatment is associated with improvement in coronary endothelial function and decreased cytokine activation in patients after heart transplantation. J Am Coll Cardiol. 2001;38:814-818.
36. Albert MA, Danielson E, Rifai N, Ridker PM. Effect of statin therapy on C-reactive protein levels: the pravastatin inflammation/CRP evaluation (PRINCE): a randomized trial and cohort study. JAMA. 2001;286:64-70.
37. Ridker PM, Rifai N, Lowenthal SP. Rapid reduction in C-reactive protein with cerivastatin among 785 patients with primary hypercholesterolemia. Circulation. 2001;103:1191-1193.
38. Ridker PM, Rifai N, Clearfield M, Downs JR, Weis SE, Miles JS, Gotto AM Jr. Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med. 2001;344:1959-1965.
39. Ridker PM, Rifai N, Pfeffer MA, Sacks F, Braunwald E. Long-term effects of pravastatin on plasma concentration of C-reactive protein: the Cholesterol and Recurrent Events (CARE) Investigators. Circulation. 1999;100:230-235.
40. Munford RS. Statins and the acute-phase response. N Engl J Med. 2001;344:2016-2018.
41. Tribble DL, Rizzo M, Chait A, Lewis DM, Blanche PJ, Krauss RM. Enhanced oxidative susceptibility and reduced antioxidant content of metabolic precursors of small, dense low-density lipoproteins. Am J Med. 2001;110:103-110.
42. Chancharme L, Therond P, Nigon F, Lepage S, Couturier M, Chapman MJ. Cholesteryl ester hydroperoxide lability is a key feature of the oxidative susceptibility of small, dense LDL. Arterioscler Thromb Vasc Biol. 1999;19:810-820.
43. Chancharme L, Therond P, Nigon F, Zarev S, Mallet A, Bruckert E, Chapman MJ. LDL particle subclasses in hypercholesterolemia: molecular determinants of reduced lipid hydroperoxide stability. J Lipid Res. 2002;43:453-462.
44. Guerin M, Lassel TS, Le Goff W, Farnier M, Chapman MJ. Action of atorvastatin in combined hyperlipidemia: preferential reduction of cholesteryl ester transfer from HDL to VLDLI particles. Arterioscler Thromb Vasc Biol. 2000;20:189-197.
45. Lindahl B, Toss H, Siegbahn A, Venge P, Wallentin L. Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary artery disease: FRISC Study Group: Fragmin During Instability in Coronary Artery Disease. N Engl J Med. 2000;343:1139-1147.
46. Kinlay S, Rifai N, Libby P, Ganz P. Effect of atorvastatin on C-reactive protein in patients with acute coronary syndromes: a substudy of the MIRACL trial. J Am Coll Cardiol. 2000;39:304A. Abstract.
47. Marmur JD, Thiruvikraman SV, Fyfe BS, Guha A, Sharma SK, Ambrose JA, Fallon JT, Nemerson Y, Taubman MB. Identification of active tissue factor in human coronary atheroma. Circulation. 1996;94:1226-1232.
48. Ardissino D, Merlini PA, Ariens R, Coppola R, Bramucci E, Mannucci PM. Tissue-factor antigen and activity in human coronary atherosclerotic plaques. Lancet. 1997;349:769-771.
49. Jang IK, Gold HK, Leinbach RC, Fallon JT, Collen D, Wilcox JN. Antithrombotic effect of a monoclonal antibody against tissue factor in a rabbit model of platelet-mediated arterial thrombosis. Arterioscler Thromb. 1992;12:948-954.
50. Pawashe AB, Golino P, Ambrosio G, Migliaccio F, Ragni M, Pascucci I, Chiariello M, Bach R, Garen A, Konigsberg WK, et al. A monoclonal antibody against rabbit tissue factor inhibits thrombus formation in stenotic injured rabbit carotid arteries. Circ Res. 1994;74:56-63.
51. Colli S, Eligini S, Lalli M, Camera M, Paoletti R, Tremoli E. Vastatins inhibit tissue factor in cultured human macrophages: a novel mechanism of protection against atherothrombosis. Arterioscler Thromb Vasc Biol. 1997;17:265-272.
52. Ferro D, Basili S, Alessandri C, Cara D, Violi F. Inhibition of tissue-factor-mediated thrombin generation by simvastatin. Atherosclerosis. 2000;149:111-116.
53. Lesnik P, Rouis M, Skarlatos S, Kruth HS, Chapman MJ. Uptake of exogenous free cholesterol induces upregulation of tissue factor expression in human monocyte-derived macrophages. Proc Natl Acad Sci U S A. 1992;89:10370-10374.
54. Rosenson RS, Lowe GD. Effects of lipids and lipoproteins on thrombosis and theology. Atherosclerosis. 1998;140:271-280.
55. Meade TW, North WR, Chakrabarti R, Stirling Y, Haines AP, Thompson SG, Brozovie M. Haemostatic function and cardiovascular death: early results of a prospective study. Lancet. 1980;1:1050-1054.
56. Meade TW, Ruddock V, Stirling Y, Chakrabarti R, Miller GJ. Fibrinolytic activity, clotting factors, and long-term incidence of ischaemic heart disease in the Northwick Park Heart Study. Lancet. 1993;342:1076-1079.
57. Hoffman CJ, Miller RH, Lawson WE, Hultin MB. Elevation of factor VII activity and mass in young adults at risk of ischemic heart disease. J Am Coll Cardiol. 1989;14:941-946.
58. Girelli D, Russo C, Ferraresi P, Olivieri O, Pinotti M, Friso S, Manzato F, Mazzucco A, Bernardi F, Corrocher R. Polymorphisms in the factor VII gene and the risk of myocardial infarction in patients with coronary artery disease. N Engl J Med. 2000;343:774-780.
59. Wu AH, Tsongalis GJ. Correlation of polymorphisms to coagulation and biochemical risk factors for cardiovascular diseases. Am J Cardiol. 2001;87:1361-1366.
60. Balleisen L, Assmann G, Bailey J, Epping PH, Schulte H, van de Loo J. Epidemiological study on factor VII, factor VIII and fibrinogen in an industrial population, II: baseline data on the relation to blood pressure, blood glucose, uric acid, and lipid fractions. Thromb Haemost. 1985;54:721-723.
61. Folsom AR, Wu KK, Davis CE, Conlan MG, Sorlie PD, Szklo M. Population correlates of plasma fibrinogen and factor VII, putative cardiovascular risk factors. Atherosclerosis. 1991;91:191-205.
62. Friedman GD, Cutter GR, Donahue RP, Hughes GH, Hulley SB, Jacobs DR Jr, Liu K, Savage PJ. CARDIA: study design, recruitment, and some characteristics of the examined subjects. J Clin Epidemiol. 1988;41:1105-1116.
63. Dujovne CA, Harris WS, Altman R, Overhiser RW, Black DM. Effect of atorvastatin on hemorheologic-hemostatic parameters and serum fibrinogen levels in hyperlipidemic patients. Am J Cardiol. 2000;85:350-353.
64. Porreca E, Di Febbo C, Amore C, Di Castelnuovo A, Baccante G, Donati MB, Cuccurullo F, Iacoviello L. Effect of lipid-lowering treatment on factor VII profile in hyperlipidemic patients. Thromb Haemost. 2000;84:789-793.
65. Wilkes HC, Meade TW, Barzegar S, Foley AJ, Hughes LO, Bauer KA, Rosenberg RD, Miller GJ. Gemfibrozil reduces plasma prothrombin fragment F1 + 2 concentration, a marker of coagulability, in patients with coronary heart disease. Thromb Haemost. 1992;67:503-506.
66. Undas A, Brummel KE, Musial J, Mann KG, Szczeklik A. Simvastatin depresses blood clotting by inhibiting activation of prothrombin, factor V, and factor XIII and by enhancing factor Va inactivation. Circulation. 2001;103:2248-2253.
67. Roque M, Reis ED, Fuster V, Padurean A, Fallon JT, Taubman MB, Chesebro JH, Badimon JJ. Inhibition of tissue factor reduces thrombus formation and intimal hyperplasia after porcine coronary angioplasty. J Am Coll Cardiol. 2000;36:2303-2310.
68. Lesnik P, Vonica A, Guerin M, Moreau M, Chapman MJ. Anticoagulant activity of tissue factor pathway inhibitor in human plasma is preferentially associated with dense subspecies of LDL and HDL and with Lp(a). Arterioscler Thromb. 1993;13:1066-1075.
69. Hansen JB, Huseby NE, Sandset PM, Svensson B, Lyngmo V, Nordoy A. Tissue-factor pathway inhibitor and lipoproteins: evidence for association with and regulation by LDL in human plasma. Arterioscler Thromb. 1994;14:223-229.
70. Stender S, Zilversmit DB. Transfer of plasma lipoprotein components and of plasma proteins into aortas of cholesterol-fed rabbits: molecular size as a determinant of plasma lipoprotein influx. Arteriosclerosis 1981;1:38-49.
71. Lesnik P, Dentan C, Vonica A, Moreau M, Chapman MJ. Tissue factor pathway inhibitor activity associated with LDL is inactivated by cell-and copper-mediated oxidation. Arterioscler Thromb Vasc Biol. 1995;15:1121-1130.
72. Pietzsch J, Lattke P, Julius U. Oxidation of apolipoprotein B-100 in circulating LDL is related to LDL residence time: in vivo insights from stable-isotope studies. Arterioscler Thromb Vasc Biol 2000;20: E63-E67.
73. Nordoy A, Bonaa KH, Sandset PM, Hansen JB, Nilsen H. Effect of omega-3 fatty acids and simvastatin on hemostatic risk factors and postprandial hyperlipemia in patients with combined hyperlipemia. Arterioscler Thromb Vasc Biol. 2000;20:259-265.
74. Sandset PM, Lund H, Norseth J, Abildgaard U, Ose L. Treatment with hydroxymethylglutaryl-coenzyme A reductase inhibitors in hypercholesterolemia induces changes in the components of the extrinsic coagulation system. Arterioscler Thromb. 1991;11:138-145.
75. Carvalho AC, Colman RW, Lees RS. Platelet function in hyperlipoproteinemia. N Engl J Med. 1974;290:434-438.
76. 2+ and membrane dynamics in patients with primary hypercholesterolemia: effects of pravastatin. Arterioscler Thromb Vasc Biol. 1995;15:759-764.
77. Notarbartolo A, Davi G, Averna M, Barbagallo CM, Ganci A, Giammarresi C, La Placa FP, Patrono C. Inhibition of thromboxane biosynthesis and platelet function by simvastatin in type IIa hypercholesterolemia. Arterioscler Thromb Vasc Biol. 1995;15:247-251.
78. Szczeklik A, Musial J, Undas A, Gajewski P, Gora P, Swadzba J, Jankowski M. Inhibition of thrombin generation by simvastatin and lack of additive effects of aspirin in patients with marked hypercholesterolemia. J Am Coll Cardiol. 1999;33:1286-293.
79. Dangas G, Badimon JJ, Smith DA, Unger AH, Levine D, Shao JH, Meraj P, Fier C, Fallon JT, Ambrose JA. Pravastatin therapy in hyperlipidemia: effects on thrombus formation and the systemic hemostatic profile. J Am Coll Cardiol. 1999;33:1294-1304.
80. Koenig W, Sund M, Ernst E, Mraz W, Hombach V, Keil U. Association between rheology and components of lipoproteins in human blood. Results from the MONICA project. Circulation. 1992;85:2197-2204.
81. Cremer P, Nagel D, Labrot B, Mann H, Muche R, Elster H, Seidel D. Lipoprotein Lp(a) as predictor of myocardial infarction in comparison to fibrinogen, LDL cholesterol and other risk factors: results from the prospective Gottingen Risk Incidence and Prevalence Study (GRIPS). Eur J Clin Invest. 1994;24:444-453.
82. Aguilar-Salinas CA, Fanghanel-Salmon G, Meza E, Montes J, Gulias-Herrero A, Sanchez L, Monterrubio-Flores EA, Gonzalez-Valdez H, Gomez Perez FJ. Ciprofibrate versus gemfibrozil in the treatment of mixed hyperlipidemias: an open-label, multicenter study. Metabolism. 2001;50:729-733.
83. de Maat MP. Effects of diet, drugs, and genes on plasma fibrinogen levels. Ann N Y Acad Sci. 2001;936:509-521.
84. Rauch U, Osende JI, Chesebro JH, Fuster V, Vorchheimer DA, Harris K, Harris P, Sandler DA, Fallon JT, Jayaraman S, Badimon JJ. Statins and cardiovascular diseases: the multiple effects of lipid-lowering therapy by statins. Atherosclerosis. 2000;153:181-189.
85. Simes RJ, Topol EJ, Holmes DR Jr, White HD, Rutsch WR, Vahanian A, Simoons ML, Morris D, Betriu A, Califf RM, et al. Link between the angiographic substudy and mortality outcomes in a large randomized trial of myocardial reperfusion: importance of early and complete infarct artery reperfusion: GUSTO-I Investigators. Circulation. 1995;91:1923-1928.
86. Epstein SE, Talbot TL. Dynamic coronary tone in precipitation, exacerbation and relief of angina pectoris. Am J Cardiol. 1981;48:797-803.
87. Gage JE, Hess OM, Murakami T, Ritter M, Grimm J, Krayenbuehl HP. Vasoconstriction of stenotic coronary arteries during dynamic exercise in patients with classic angina pectoris: reversibility by nitroglycerin. Circulation. 1986;73:865-876.
88. Kaski JC, Tousoulis D, Gavrielides S, McFadden E, Galassi AR, Crea F, Maseri A. Comparison of epicardial coronary artery tone and reactivity in Prinzmetal's variant angina and chronic stable angina pectoris. J Am Coll Cardiol. 1991;17:1058-1062.
89. Cox DA, Vita JA, Treasure CB, Fish RD, Alexander RW, Ganz P, Selwyn AP. Atherosclerosis impairs flow-mediated dilation of coronary arteries in humans. Circulation. 1989;80:458-465.
90. Brown BG, Bolson EL, Dodge HT. Dynamic mechanisms in human coronary stenosis. Circulation. 1984;70:917-922.
91. Pries AR, Secomb TW, Gaehtgens P. Structural adaptation and stability of microvascular networks: theory and simulations. Am J Physiol. 1998;275:H349-H360.
92. Kern MJ. Coronary physiology revisited: practical insights from the cardiac catheterization laboratory. Circulation. 2000;101:1344-1351.
93. Fragasso G, Rossetti E, Dosio F, Gianolli L, Pizzetti G, Cattaneo N, Fazio F, Chierchia SL. High prevalence of the thallium-201 reverse redistribution phenomenon in patients with syndrome X. Eur Heart J. 1996;17:1482-1487.
94. Mansur AP, Serrano CV Jr, Nicolau JC, Cesar LA, Ramires JA. Effect of cholesterol lowering treatment on positive exercise tests in patients with hypercholesterolaemia and normal coronary angiograms. Heart. 1999;82:689-693.
95. Murakami H, Urabe K, Nishimura M. Inappropriate microvascular constriction produced transient ST-segment elevation in patients with syndrome X. J Am Coll Cardiol. 1998;32:1287-1294.
96. Mathier MA, Rose GA, Fifer MA, Miyamoto MI, Dinsmore RE, Castano HH, Dec GW, Palacios IF, Semigran MJ. Coronary endothelial dysfunction in patients with acute-onset idiopathic dilated cardiomyopathy. J Am Coll Cardiol. 1998;32:216-224.
97. Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992;340:1111-1115.
98. Egashira K, Inou T, Hirooka Y, Yamada A, Maruoka Y, Kai H, Sugimachi M, Suzuki S, Takeshita A. Impaired coronary blood flow response to acetylcholine in patients with coronary risk factors and proximal atherosclerotic lesions. J Clin Invest. 1993;91:29-37.
99. Mangin EL Jr, Kugiyama K, Nguy JH, Kerns SA, Henry PD. Effects of lysolipids and oxidatively modified low density lipoprotein on endothelium-dependent relaxation of rabbit aorta. Circ Res. 1993;72:161-166.
100. Pritchard KA Jr, Groszek L, Smalley DM, Sessa WC, Wu M, Villalon P, Wolin MS, Stemerman MB. Native low-density lipoprotein increases endothelial cell nitric oxide synthase generation of superoxide anion. Circ Res. 1995;77:510-518.
101. O'Driscoll G, Green D, Taylor RR. Simvastatin, an HMG-coenzyme A reductase inhibitor, improves endothelial function within I month. Circulation. 1997;95:1126-1131.
102. Tamai O, Matsuoka H, Itabe H, Wada Y, Kohno K, Imaizumi T. Single LDL apheresis improves endothelium-dependent vasodilatation in hypercholesterolemic humans. Circulation. 1997;95:76-82.
103. Sposito AC, Mansur AP, Coelho OR, Nicolau JC, Ramires JA. Additional reduction in blood pressure after cholesterol-lowering treatment by statins (lovastatin or pravastatin) in hypercholesterolemic patients using angiotensin-converting enzyme inhibitors (enalapril or lisinopril). Am J Cardiol. 1999;83:1497-1499.
104. Ramires JA, Sposito AC, Mansur AP, Coelho OR, Maranhao M, Cesar LA. Cholesterol lowering with statins reduces exercise-induced myocardial ischemia in hypercholesterolemic patients with coronary artery disease. Am J Cardiol. 2001;88:1134-1138.
105. Liao JK, Shin WS, Lee WY, Clark SL. Oxidized low-density lipoprotein decreases the expression of endothelial nitric oxide synthase. J Biol Chem. 1995;270:319-324.
106. Laufs U, La Fata V, Plutzky J, Liao JK. Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation. 1998;97:1129-1135.
107. Wagner AH, Kohler T, Ruckschloss U, Just I, Hecker M. Improvement of nitric oxide-dependent vasodilatation by HMG-CoA reductase inhibitors through attenuation of endothelial superoxide anion formation. Arterioscler Thromb Vasc Biol. 2000;20:61-69.
108. Hernandez-Perera O, Perez-Sala D, Navarro-Antolin J, Sanchez-Pascuala R, Hernandez G, Diaz C, Lamas S. Effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, atorvastatin and simvastatin, on the expression of endothelin-1 and endothelial nitric oxide synthase in vascular endothelial cells. J Clin Invest. 1998;101:2711-2719.
109. 2+ responses in rat A10 vascular smooth muscle cells. Circ Res. 1994;74:173-181.
110. Walter DH, Rittig K, Bahlmann FH, Kirchmair R, Silver M, Murayama T, Nishimura H, Losordo DW, Asahara T, Isner JM. Statin therapy accelerates reendothelialization: a novel effect involving mobilization and incorporation of bone marrow-derived endothelial progenitor cells. Circulation. 2002;105:3017-3024.
111. Coffer PJ, Jin J, Woodgett JR. Protein kinase B (c-Akt): a multifunctional mediator of phosphatidylinositol 3-kinase activation. Biochem J. 1998;335:1-13.
112. Dimmeler S, Aicher A, Vasa M, Mildner-Rihm C, Adler K, Tiemann M, Rutten H, Fichtlscherer S, Martin H, Zeiher AM. HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway. J Clin Invest. 2001;108:391-397.
113. Vasa M, Fichtlscherer S, Adler K, Aicher A, Martin H, Zeiher AM, Dimmeler S. Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease. Circulation. 2001;103:2885-2890.
114. Dimmeler S, Fleming I, Fisslthaler B, Hermann C, Busse R, Zeiher AM. Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature. 1999;399:601-605.
115. Fulton D, Gratton JP, McCabe TJ, Fontana J, Fujio Y, Walsh K, Franke TF, Papapetropoulos A, Sessa WC. Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature. 1999;399:597-601.
116. Luo Z, Fujio Y, Kureishi Y, Rudic RD, Daumerie G, Fulton D, Sessa WC, Walsh K. Acute modulation of endothelial Akt/PKB activity alters nitric oxide-dependent vasomotor activity in vivo. J Clin Invest. 2000;106:493-499.
117. Uren NG, Crake T, Lefroy DC, de Silva R, Davies GJ, Maseri A. Reduced coronary vasodilator function in infarcted and normal myocardium after myocardial infarction. N Engl J Med. 1994;331:222-227.
118. Bhagat K. Endothelial function and myocardial infarction. Cardiovasc Res. 1998;39:312-317.
119. Dupuis J, Tardif JC, Cemacek P, Theroux P. Cholesterol reduction rapidly improves endothelial function after acute coronary syndromes: the RECIFE (reduction of cholesterol in ischemia and function of the endothelium) trial. Circulation. 1999;99:3227-3233.
120. Anderson TJ, Uehata A, Gerhard MD, Meredith IT, Knab S, Delagrange D, Lieberman EH, Ganz P, Creager MA, Yeung AC, et al. Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol. 1995;26:1235-1241.
121. Bogaty P, Hackett D, Davies G, Maseri A. Vasoreactivity of the culprit lesion in unstable angina. Circulation. 1994;90:5-11.
122. Schachinger V, Britten MB, Zeiher AM. Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation. 2000;101:1899-1906.
123. Suwaidi JA, Hamasaki S, Higano ST, Nishimura RA, Holmes DR Jr, Lerman A. Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation. 2000;101:948-954.
124. Moncada S, Higgs EA. Molecular mechanisms and therapeutic strategies related to nitric oxide. FASEB J. 1995;9:1319-1330.
125. Vane JR, Anggard EE, Botting RM. Regulatory functions of the vascular endothelium. N Engl J Med. 1990;323:27-36.
126. Forman MB, Puett DW, Virmani R. Endothelial and myocardial injury during ischemia and reperfusion: pathogenesis and therapeutic implications. J Am Coll Cardiol. 1989;13:450-459.
127. Tsao PS, Aoki N, Lefer DJ, Johnson G III, Lefer AM. Time course of endothelial dysfunction and myocardial injury during myocardial ischemia and reperfusion in the cat. Circulation. 1990;82:1402-1412.
128. Weiss SJ. Tissue destruction by neutrophils. N Engl J Med. 1989;320:365-376.
129. Engler RL, Schmid-Schonbein GW, Pavelec RS. Leukocyte capillary plugging in myocardial ischemia and reperfusion in the dog. Am J Pathol. 1983;111:98-111.
130. Lefer AM, Campbell B, Shin YK, Scalia R, Hayward R, Lefer DJ. Simvastatin preserves the ischemic-reperfused myocardium in normocholesterolemic rat hearts. Circulation. 1999;100:178-184.
131. Di Napoli P, Antonio Taccardi A, Grilli A, Spina R, Felaco M, Barsotti A, De Caterina R. Simvastatin reduces reperfusion injury by modulating nitric oxide synthase expression: an ex vivo study in isolated working rat hearts. Cardiovasc Res. 2001;51:283-293.
132. Stenestrand U, Wallentin L. Early statin treatment following acute myocardial infarction and 1-year survival. JAMA. 2001;285:430-436.
133. Aronow HD, Topol EJ, Roe MT, Houghtaling PL, Wolski KE, Lincoff AM, Harrington RA, Califf RM, Ohman EM, Kleiman NS, Keltai M, Wilcox RG, Vahanian A, Armstrong PW, Lauer MS. Effect of lipid-lowering therapy on early mortality after acute coronary syndromes: an observational study. Lancet. 2001;357:1063-1068.
134. Schwartz GG, Olsson AG, Ezekowitz MD, Ganz P, Oliver MF, Waters D, Zeiher A, Chaitman BR, Leslie S, Stern T; Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study Investigators. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA. 2001;285:1711-1718.
135. Sandercock P. Statins for stroke prevention? Lancet. 2001;357:1548-1549.
136. Jick H, Zomberg GL, Jick SS, Seshadri S, Drachman DA. Statins and the risk of dementia. Lancet. 2000;356:1627-1631.
137. Callahan A. Cerebrovascular disease and statins: a potential addition to the therapeutic armamentarium for stroke prevention. Am J Cardiol. 2001;88:33J-37J.
138. Muhlestein JB, Home BD, Bair TL, Li Q, Madsen TE, Pearson RR, Anderson JL. Usefulness of in-hospital prescription of statin agents after angiographic diagnosis of coronary artery disease in improving continued compliance and reduced mortality. Am J Cardiol. 2001;87:257-261.