Basic science review: Statin therapy-part I: The pleiotropic effects of statins in cardiovascular disease

Vascular and Endovascular Surgery

Volumn 44, Issue 4, 2010, Pages 241-251

  Sadowitz, Benjamin ^a,b   Maier, Kristopher G ^a,b   Gahtan, Vivian ^a,b  

^a SUNY UPSTATE MEDICAL UNIVERSITY   (United States)

^b VA Healthcare Network Upstate New York   (United States)

Author keywords

Cardiovascular disease; Hypercholesterolemia; Pleiotropic; Statins

Indexed keywords

ATORVASTATIN; CERIVASTATIN; ENDOTHELIAL NITRIC OXIDE SYNTHASE; FLUINDOSTATIN; GUANINE NUCLEOTIDE BINDING PROTEIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; ISOPRENOID; LIPOPROTEIN; MANUMYCIN; MEVALONIC ACID; MEVINOLIN; OXIDIZED LOW DENSITY LIPOPROTEIN; PITAVA; PITAVASTATIN; PRAVASTATIN; RAS PROTEIN; RHO GUANINE NUCLEOTIDE BINDING PROTEIN; ROSUVASTATIN; SIMVASTATIN; UNCLASSIFIED DRUG;

ARTERY INTIMA PROLIFERATION; ATHEROSCLEROSIS; ATHEROSCLEROTIC PLAQUE; ATTENUATION; BLOOD VESSEL WALL; CARDIOVASCULAR DISEASE; CELL FUNCTION; CELL MIGRATION; CELL PROLIFERATION; ENDOTHELIUM CELL; ENDOTHELIUM INJURY; HUMAN; HYPERCHOLESTEROLEMIA; NONHUMAN; PLEIOTROPY; REVIEW; SMOOTH MUSCLE FIBER; THROMBOCYTE; THROMBOCYTE ACTIVATION; THROMBOCYTE AGGREGATION; VASCULAR SMOOTH MUSCLE; VASCULITIS;

ATHEROSCLEROSIS; BIOLOGICAL MARKERS; BLOOD PLATELETS; CARDIOVASCULAR AGENTS; CARDIOVASCULAR DISEASES; CHOLESTEROL; DISEASE PROGRESSION; ENDOTHELIAL CELLS; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; HYPERCHOLESTEROLEMIA; INFLAMMATION; MUSCLE, SMOOTH, VASCULAR; TREATMENT OUTCOME;

EID: 77951716673     PISSN: 15385744     EISSN: None     Source Type: Journal    
DOI: 10.1177/1538574410362922     Document Type: Review

References (117)

1. Buhaescu I., Izzedine H. Mevalonate pathway: a review of clinical and therapeutical implications. Clin Biochem. 2007 ; 40 (9-10). 575-584.
2. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study. Lancet. 1994 ; 344 (8934). 1383-1389.
3. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998 ; 339 (19). 1349-1357.
4. Downs JR, Clearfield M., Weis S., et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. JAMA. 1998 ; 279 (20). 1615-1622.
5. Sever PS, Dahlof B., Poulter NR, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA): a multicenter randomized controlled trial. Lancet. 2003 ; 361 (9364). 1149-1158. (Pubitemid 36398384)
6. Shepherd J., Cobbe SM, Ford I., et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med. 1995 ; 333 (20). 1301-1307.
7. Group Heart Protection Study Collaborative. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002 ; 360 (9326). 7-22.
8. Almuti K., Rimawi R., Spevack D., et al. Effects of statins beyond lipid lowering: Potential for clinical benefits. Int J Cardiol. 2006 ; 109 (1). 7-15.
9. Liao JK Clinical implications for statin pleiotropy. Curr Opin Lipidol. 2005 ; 16 (6). 624-629.
10. Labios M., Martinez M., Gabriel F., Guiral V., Martànez E., Aznar J. Effect of atorvastatin upon platelet activation in hypercholesterolemia, evaluated by flow cytometry. Thromb Res. 2005 ; 115 (4). 263-270.
11. Huhle G., Abletshauser C., Mayer N., Weidinger G., Harenberg J., Heene DL Reduction of platelet activity markers in type II hypercholesterolemic patients by a HMG-CoA-reductase inhibitor. Thromb Res. 1999 ; 95 (5). 229-234.
12. Haramaki N., Ikeda H., Takenaka K., et al. Fluvastatin alters platelet aggregability in patients with hypercholesterolemia: possible improvement of intraplatelet redox via HMG-CoA reductase. Arterioscler Thromb Vasc Biol. 2007 ; 27 (6). 1471-1478.
13. Hussein O., Rosenblat M., Schlezinger S., Shlomo K., Michael A. Reduced platelet aggregation after fluvastatin therapy is associated with altered platelet lipid composition and drug binding to platelets. Br J Clin Pharmacol. 1997 ; 44 (1). 77-83.
14. Laufs U., La Fata V., Plutzky J., et al. Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation. 1998 ; 97 (12). 1129-1135.
15. Laufs U., La Fata V., Liao JK Inhibition of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase blocks hypoxia-mediated down-regulation of endothelial nitric oxide synthase. J Biol Chem. 1997 ; 272 (50). 31725-31729.
16. Rikitake Y., Kawashima S., Takeshita S., et al. Anti-oxidative properties of fluvastatin, an HMG-CoA reductase inhibitor, contribute to prevention of atherosclerosis in cholesterol-fed rabbits. Atherosclerosis. 2001 ; 154 (1). 87-96.
17. Dimmeler S., Aicher A., Vasa M., et al. HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI3-kinase/Akt pathway. J Clin Invest. 2001 ; 108 (3). 391-397.
18. Assmus B., Urbich C., Aicher A., et al. HMG-CoA reductase inhibitors reduce senescence and increase proliferation of endothelial progenitor cells via regulation of the cell cycle regulatory genes. Circ Res. 2003 ; 92 (9). 1049-1055.
19. Spyridopoulos I., Haendeler J., Urbich C., et al. Statins enhance migratory capacity by upregulation of the telomere repeat-binding factor TRF2 in endothelial progenitor cells. Circulation. 2004 ; 110 (19). 3136-3142.
20. Llevadot J., Murasawa S., Kureishi Y., et al. HMG-CoA reductase inhibitor mobilizes bone marrow-derived endothelial progenitor cells. J Clin Invest. 2001 ; 108 (3). 399-405.
21. Porter KE, Naik J., Turner NA, Dickinson T., Thompson MM, London NJ et al. Simvastatin inhibits human saphenous vein neointima formation via inhibition of smooth muscle cell proliferation and migration. Journal of Vascular Surgery. 2002 ; 36 (1). 150-157.
22. Guijarro C., Blanco-Colio LM, Ortego M., et al. 3-Hydroxy-3- methylglutaryl coenzyme A reductase and isoprenylation inhibitors induce apoptosis of vascular smooth muscle cells in culture. Circulation Research. 1998 ; 83 (5). 490-500.
23. Kaneider NC, Reinisch CM, Dunzendorger S., Meierhofer C., Djanani A., Wiedermann CJ et al. Induction of apoptosis and inhibition of migration of inflammatory and vascular wall cells by cerivastatin. Atherosclerosis. 2001 ; 158 (1). 23-33.
24. Erl W., Hristov M., Neureuter M., Yan ZQ, Hansson GK, Weber PC et al. HMG-CoA reductase inhibitors induce apoptosis in neointima-derived vascular smooth muscle cells. Atherosclerosis. 2003 ; 169 (2). 251-258.
25. Senokuchi T., Matsumura T., Sakai M., et al. Statins suppress oxidized low density lipoprotein-induced macrophage proliferation by inactivation of the small G protein-p38 MAPK pathway. J Biol Chem. 2005 ; 280 (8). 6627-6633.
26. Aikawa M., Rabkin E., Sugiyama S., et al. An HMG-CoA reductase inhibitor, cerivastatin, suppresses growth of macrophages expressing matrix metalloproteinases and tissue factor in vivo and in vitro. Circulation. 2001 ; 103 (2). 276-283.
27. 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 (7). 926-933.
28. Draude G., Hrboticky N., Lorenz RL The expression of the lectin-like oxidized low-density lipoprotein receptor (LOX-1) on human vascular smooth muscle cells and monocytes and its downregulation by lovastatin. Biochem Pharmacol. 1999 ; 57 (4). 383-386.
29. Pietsch A., Erl W., Lorenz RL Lovastatin reduces expression of the combined adhesion and scavenger receptor CD36 in human monocytic cells. Biochem Pharmacol. 1996 ; 52 (3). 433-439.
30. Umetani N., Kanayama Y., Okamura M., et al. Lovastatin inhibits gene expression of type-1 scavenger receptor in THP-1 human macrophages. Biochim Biophys Acta. 1996 ; 1303 (3). 199-206.
31. Kwak B., Mulhaupt F., Myit S., Mach F. Statins as a newly recognized type of immunomodulator. Nat Med. 2000 ; 6 (12). 1399-1402.
32. Ridker PM, Rifai N., Lowenthal SP Rapid reduction in C-reactive protein with cerivastatin among 785 patients with primary hypercholesterolemia. Circulation. 2001 ; 103 (9). 1191-1193.
33. Ridker PM, Rifai N., Clearfield M., et al. Measurement of Creactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med. 2001 ; 344 (26). 1959-1965.
34. Ridker PM, Rifai N., Clearfield M., Sacks F., Braunwald E. Long-term effects of pravastatin on plasma concentration of C-reactive protein. Circulation. 1999 ; 100 (3). 230-235.
35. Kuoppala J., Lamminpaa A., Pukkala E. Statins and cancer: a systematic review and meta-analysis. Eur J Cancer. 2008 ; 44 (15). 2122-2132.
36. Wong TY, Rogers SL Statins and age-related macular degeneration: time for a randomized controlled trial ? Am J Ophthalmol. 2007 ; 144 (1). 117-119.
37. Falagas M., Makris GC, Matthaiou DK, Rafailidis PI Statins for infection and sepsis: a systematic review of the clinical evidence. J Antimicrob Chemother. 2008 ; 61 (4). 774-785.
38. Biskobing DM, Novy AM, Downs R. Jr. Novel therapeutic options for osteoporosis. Curr Opin Rheumatol. 2002 ; 14 (4). 447-452.
39. Liao JK, Laufs U. Pleiotropic effects of statins. Ann Rev Pharmacol Toxicol. 2005 ; 45: 89-118.
40. Calabro P., Yeh ETH. The pleiotropic effects of statins. Curr Opin Cardiol. 2005 ; 20 (6). 541-547.
41. Takemoto M., Liao JK Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Arterioscler Thromb Vasc Biol. 2001 ; 21 (11). 1712-1719.
42. Schachter M. Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update. Fundam Clin Pharmacol. 2005 ; 19 (1). 117-125.
43. McTaggart F., Buckett L., Davidson R., et al. Preclinical and clinical pharmacology of Rosuvastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. Am J Cardiol. 2001 ; 87 (5A). 28B - 32B.
44. McTavish D., Sorkin EM Pravastatin: a review of its pharmacological properties and therapeutic potential in hypercholesterolemia. Drugs. 1991 ; 42 (1). 65-89.
45. Nezasa K., Higaki K., Takeuchi M., Nakano M., Koike M. Uptake of rosuvastatin by isolated rat hepatocytes: comparison with pravastatin. Xenobiotica. 2003 ; 33 (4). 379-388.
46. Rosenson RS, Tangney CC Antiatherothrombotic properties of statins: implications for cardiovascular event reduction. JAMA. 1998 ; 279 (20). 1643-1650.
47. Hamelin B., Turgeon J. Hydrophilicity/lipophilicity: relevance for the pharmacology and clinical effects of HMG-CoA reductase inhibitors. Trends Pharmacol Sci. 1998 ; 19 (1). 26-37.
48. Ziegler K., Hummelsiep S. Hepatoselective carrier-mediated sodium-independent uptake of pravastatin and pravastatin-lactone. Biochim Biophys Acta. 1993 ; 1153 (1). 23-33.
49. van Vliet Ak, van Thiel GC, Huisman RH, Moshage H., Yap SH, Cohen LH Different effects of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors on sterol synthesis in various human cells types. Biochim Biophys Acta. 1995 ; 1254 (1). 105-111.
50. Corsini A., Bernini F., Quarato P., et al. Non-lipid-related effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Cardiology. 1996 ; 87 (6). 458-468.
51. van Vliet AK, Negre-Aminou P., van Thiel GCF, Bolhuis PA, Cohen LH Action of lovastatin, simvastatin, and pravastatin on sterol synthesis and their antiproliferative effect in cultured myoblasts from human striated muscle. Biochem Pharmacol. 1996 ; 52 (9). 1387-1392.
52. Ross R. Atherosclerosis-an inflammatory disease. N Engl J Med. 1999 ; 340 (2). 115-126.
53. Ruggeri ZM Platelets in atherothrombosis. Nat Med. 2002 ; 8 (11). 1227-1234.
54. Siegel-Axel D., Daub K., Seizer P., Lindemann S., Gawaz M. Platelet lipoprotein interplay: trigger of foam cell formation and driver of atherosclerosis. Cardiovasc Res. 2008 ; 78 (1). 8-17.
55. Lumsden AB, Lin PH, Bush RL, Chen C. Schwartzs Principles of Surgery. 8 th ed. New York, NY: McGraw-Hill Companies ; 2005.
56. Jonasson L., Holm J., Skalli O., Bondjers G., Hansson GK Regional accumulations of T cells, macrophages, and smooth muscle cells in the human atherosclerotic plaque. Arteriosclerosis. 1986 ; 6 (2). 131-138.
57. Kokubo T., Uchida H., Choi ET Integrin alphavbeta3 as a target in the prevention of neointimal hyperplasia. J Vasc Surg. 2007 ; 45 (suppl A). 33A - 38A.
58. Kirchengast M., Munter K. Endothelin and restenosis. Cardiovasc Res. 1998 ; 39 (3). 550-555.
59. Wu CH, Lin CS, Hung JS, et al. Inhibition of neointimal formation in porcine coronary artery by a ras mutant. J Surg Res. 2001 ; 99 (1). 100-106.
60. Serruys PW, Luijten HE, Beatt KJ, et al. Incidence of restenosis after successful coronary angioplasty: a time-related phenomenon. Circulation. 1988 ; 77 (2). 361-371.
61. Schwartz RS, Holmes DR Jr, Topol EJ The restenosis paradigm revisited: an alternative proposal for cellular mechanisms. J Am Coll Cardiol. 1992 ; 20 (5). 1284-1293.
62. National Institutes of Health National Heart, Lung, and Blood Institute. National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III).
63. Goldstein JL, Brown MS Regulation of the mevalonate pathway. Nature. 1990 ; 343 (6257). 425-430.
64. Wong WW-L, Dimitroulakos J., Minden MD, Penn LZ HMGCoA reductase inhibitors and the malignant cell: the statin family of drugs as triggers of tumor-specific apoptosis. Leukemia. 2002 ; 16 (4). 508-519.
65. Adamson P., Marshall CJ, Hall A., Tilbrook PA Post-translational modifications of p21rho proteins. J Biol Chem. 1992 ; 267 (28). 20033-20038.
66. Vincent L., Soria C., Mirshahi F., et al. Cerivastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme a reductase, inhibits endothelial cell proliferation induced by angiogenic factors in vitro and angiogenesis in in vivo models. Arterioscler Thromb Vasc Biol. 2002 ; 22 (4). 623-629.
67. Argmann CA, Edwards JY, Sawyez CG, et al. Regulation of macrophage cholesterol efflux through hydroxymethylglutarylCoA reductase inhibition. J Biol Chem. 2005 ; 280 (23). 22212-22221.
68. Casey PJ Protein lipidation in cell signaling. Science. 1995 ; 268 (5208). 221-225.
69. Shirai H., Autieri M., Eguchi S. Small GTP-binding proteins and mitogen-activated protein kinases as promising therapeutic targets of vascular remodeling. Curr Opin Nephrol Hypertens. 2007 ; 16 (2). 111-115.
70. Kouchi H., Nakamure K., Fushimi K., et al. Manumycin A, inhibitor of ras farnesyltransferase, inhibits proliferation and migration of rat vascular smooth muscle cells. Biochem Biophys Res Commun. 1999 ; 264 (3). 915-920.
71. Sugita M., Sugita H., Kaneki M. Farnesyltransferase inhibitor, manumycin A, prevents atherosclerosis development and reduces oxidative stress in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2007 ; 27 (6). 1390-1395.
72. Indolfi C., Avvedimento EV, Rapacciuolo A., et al. Inhibition of cellular ras prevents smooth muscle cell proliferation after vascular injury in vivo. Nat Med. 1995 ; 1 (6). 541-545.
73. Jin G., Wu JCH, Li YS, Hu YL, Shyy JY, Chien S. Effects of active and negative mutants of ras on rat arterial neointima formation. J Surg Res. 2000 ; 94 (2). 124-132.
74. Heasman SJ, Ridley AJ Mammalian Rho GTPases: new insights into their functions from in vivo studies. Nature. 2008 ; 9 (9). 690-701.
75. Van Aelst L., Souza-Schorey C. Rho GTPases and signaling networks. Genes Dev. 1997 ; 11 (18). 2295-2322.
76. Laufs U., Marra D., Node K., Liao JK 3-Hydroxy-3-methylglutarylCoA reductase inhibitors attenuate vascular smooth muscle proliferation by preventing Rho GTPase-induced down-regulation of p27. J Biol Chem. 1999 ; 274 (31). 21926-21931.
77. Eto M., Barandier C., Rathgeb L., et al. Thrombin suppresses endothelial nitric oxide synthase and upregulates endothelin-converting enzyme by distinct pathways: role of Rho/ROCK and mitogen-activated protein kinase. Circ Res. 2001 ; 89 (7). 583-590.
78. Laufs U., Liao JK Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by Rho GTPase. J Biol Chem. 1998 ; 273 (37). 24266-24271.
79. Aviram M., Hussein O., Rosenblat M., Schlezinger S., Hayek T., Keidar S. Interactions of platelets, macrophages, and lipoproteins in hypercholesterolemia: antiatherogenic effects of HMG-CoA reductase inhibitor therapy. J Cardiovasc Pharmacol. 1998 ; 31 (1). 39-45.
80. Abrams C., Shattil SJ Immunological detection of activated platelets in clinical disorders. Thromb Haemost. 1991 ; 65 (5). 467-473.
81. Carvalho AC, Colmanm RW, Lees RS Platelet function in hyperlipoproteinemia. N Engl J Med. 1974 ; 290 (8). 434-438.
82. Hochgraf E., Levy Y., Aviram M., Brook JG, Cogan U. Lovastatin decreases plasma and platelet cholesterol levels and normalizes elevated platelet fluidity and aggregation in hypercholesterolemic patients. Metabolism. 1994 ; 43 (1). 11-17.
83. Shattil SJ, Anaya-Galindo R., Bennett J., Colman RW, Cooper RA Platelet hypersensitivity induced by cholesterol incorporation. J Clin Invest. 1975 ; 55 (3). 636-643.
84. Relou IAM, Hackeng CM, Akkerman JWN, Malle E. Low-density lipoprotein and its effect on human blood platelets. Cell Mol Life Sci. 2003 ; 60 (5). 961-971.
85. Aviram M., Brook JG Platelet interaction with high and low density lipoproteins. Atherosclerosis. 1983 ; 46 (3). 259-268.
86. Schror K., Lobel P., Steinhagen-Thiessen E. Simvastatin reduces platelet thromboxane formation and restores normal platelet sensitivity against prostacyclin in type IIa hypercholesterolemia. Eicosanoids. 1989 ; 2 (1). 39-45.
87. Tsakiris DA, Keller U., Zulewshi H., Miserez AR, Wolf F., Marbet GA Simvastatin reduces activation of normal platelets by LDL isolated from patients with familial hypercholesterolemia and familial defective apolipoprotein B. Eur J Clin Pharmacol. 1997 ; 53 (3-4). 277-279.
88. Notarbartolo A., Davi G., Averna M., et al. Inhibition of thromboxane biosynthesis and platelet function by simvastatin in type IIa hypercholesterolemia. Arterioscler Thromb Vasc Biol. 1995 ; 15 (2). 247-251.
89. Matsuura E., Hughes GRV, Khamashta MA Oxidation of LDL and its clinical implication. Autoimmun Rev. 2008 ; 7 (7). 558-566.
90. Steinberg D. Oxidative modification of LDL and atherogenesis. Circulation. 1997 ; 95 (4). 1062-1071.
91. Quinn MT, Parthasarathy S., Fong LG, Steinberg D. Oxidatively modified low density lipoproteins: a potential role in recruitment and retention of monocyte/macrophages during atherogenesis. Proc Natl Acad Sci U S A. 1987 ; 84 (9). 2995-2998.
92. McMurray HF, Parthasarathy S., Steinberg D. Oxidatively modified low density lipoprotein is a chemoattractant for human T lymphocytes. J Clin Invest. 1993 ; 92 (2). 1004-1007.
93. Hessler JR Lipoprotein oxidation and lipoprotein-induced cytotoxicity. Arteriosclerosis. 1983 ; 3 (3). 215-222.
94. Li DY, Chen HJ, Mehta JL Statins inhibit oxidized-LDLmediated LOX-1 expression, uptake of oxidized-LDL and reduction in PKB phosphorylation. Cardiovasc Res. 2001 ; 52 (1). 130-135.
95. Sumpio BE, Riley JT, Dardik A. Cells in focus: endothelial cell. Int J Biochem Cell Biol. 2002 ; 34 (12). 1508-1512.
96. Beckman JA, Creager MA The nonlipid effects of statins on endothelial function. Trends Cardiovasc Med. 2006 ; 16 (5). 156-162.
97. Tesfamariam B. The effects of HMG-CoA reductase inhibitors on endothelial function. Am J Cardiovasc Drugs. 2006 ; 6 (2). 115-120.
98. Moncada S., Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med. 1993 ; 329 (27). 2002-2012.
99. Garg UC, Hassid A. Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J Clin Invest. 1989 ; 83 (5). 1774-1777.
100. Radomski MW, Palmer RMJ, Moncada S. An L-arginine/nitric oxide pathway present in human platelets regulates aggregation. Proc Natl Acad Sci. 1990 ; 87 (13). 5193-5197.
101. Tsao PS, McEvoy LM, Drexler H., Butcher EC, Cooke JP Enhanced endothelial adhesiveness in hypercholesterolemia is attenuated by L-arginine. Circulation. 1994 ; 89 (5). 2176-2182.
102. Munzel T., Sayegh H., Freeman BA, Tarpey MM, Harrison DG Evidence for enhanced vascular superoxide anion production in nitrate tolerance. J Clin Invest. 1994 ; 95 (1). 187-194.
103. Harrison DG Cellular and molecular mechanisms of endothelial cell dysfunction. J Clin Invest. 1997 ; 100 (9). 2153-2157.
104. Jaschke B., Michaelis C., Milz S., et al. Local statin therapy differentially interferes with smooth muscle and endothelial cell proliferation and reduces neointima on a drug-eluting stent platform. Circ Res. 2005 ; 68 (3). 483-492.
105. Han DKM, Haudenschild CC, Hong MK, Tinkle BT, Leon MB, Liau G. Evidence for apoptosis in human atherogenesis and in a rat vascular injury model. Am J Pathol. 1995 ; 147 (2). 267-277.
106. Libby P. Molecular bases of the acute coronary syndromes. Circulation. 1995 ; 91 (11). 2844-2850.
107. Zhou X., Nicoletti A., Elhage R., Hansson GK Transfer of CD4+ T cells aggravates atherosclerosis in immunodeficient apolipoprotein E knockout mice. Circulation. 2000 ; 102 (24). 2919-2922.
108. Lutgens E., Daemen MJAP. CD40-CD40L interactions in atherosclerosis. Trend Cardiovasc Med. 2002 ; 12 (1). 27-32.
109. Mach F., Schonbeck U., Sukhova GK, Atkinson E., Libby P. Reduction of atherosclerosis in mice by inhibition of CD40 signaling. Nature. 1998 ; 394 (6689). 200-203.
110. Mulhaupt F., Matter CM, Kwak BR, et al. Stains (HMG-CoA reductase inhibitors) reduce CD40 expression in human vascular cells. Cardiovasc Res. 2003 ; 59: 755-766.
111. Araujo JP, Lourenco P., Azevedo A., et al. Prognostic value of high-sensitivity C-reactive protein in heart failure: a systematic review. J Card Fail. 2009 ; 15 (3). 256-266.
112. Shah PK Mechanisms of plaque vulnerability and rupture. J Am Coll Cardiol. 2003 ; 41 (4 suppl S). 15S - 22S.
113. Koh KK Effects of statins on vascular wall: vasomotor function, inflammation, and plaque stability. Cardiovasc Res. 2000 ; 47 (4). 648-657.
114. Shah PK, Falk E., Badimon JJ, et al. Human monocyte-derived macrophages induce collagen breakdown in fibrous caps of atherosclerotic plaques: potential role of matrix-degrading metalloproteinases and implications for plaque rupture. Circulation. 1995 ; 92 (6). 1565-1569.
115. Libby P., Geng YJ, Aikawa M., et al. Macrophages and atherosclerotic plaque stability. Curr Opin Lipidol. 1996 ; 7 (5). 330-335.
116. 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 (6). 2493-2503.
117. Aikawa M., Rabkin E., Okada Y., et al. Lipid lowering by diet reduces matrix metalloproteinase activity and increases collagen content of rabbit atheroma: a potential mechanism of lesion stabilization. Circulation. 1998 ; 97 (24). 2433-2444.