Brief Review |
From the Cardiovascular Division, Department of Medicine, Brigham & Womens Hospital and Harvard Medical School, Boston, Mass.
Correspondence to Dr James K. Liao, Brigham & Womens Hospital, 221 Longwood Ave, LMRC-322, Boston, MA 02115. E-mail jliao{at}rics.bwh.harvard.edu
| Abstract |
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Key Words: endothelium vascular smooth muscle platelets atherosclerosis inflammation
| Introduction |
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Because serum cholesterol levels are strongly associated with coronary atherosclerotic disease,12 it has been generally assumed that cholesterol reduction by statins is the predominant, if not the only, mechanism underlying their beneficial effects in cardiovascular diseases. However, subgroup analyses of large clinical trials have challenged this notion and have suggested that the beneficial effects of statins may extend to mechanisms beyond cholesterol reduction. For example, subgroup analysis of the West of Scotland Coronary Prevention (WOSCOP) and Cholesterol and Recurrent Events (CARE) studies indicates that despite comparable serum cholesterol levels among the statin-treated and placebo groups, statin-treated individuals have a significantly lower risk of coronary heart disease than do age-matched placebo-controlled individuals.8,9,13,14 Furthermore, meta-analyses of cholesterol-lowering trials suggest that the risk of myocardial infarction in individuals treated with statins is significantly lower than that in individuals treated with other cholesterol-lowering agents or modalities despite comparable reduction in serum cholesterol levels in both groups.15,16 These findings suggest that statins may have beneficial effects beyond cholesterol lowering.
Further evidence in support of the noncholesterol benefits of statin therapy is provided by angiographic trials, which have demonstrated clinical improvements with statins that far exceed changes in the size of atherosclerotic lesions. For example, in the Familial Atherosclerosis Treatment Study (FATS) trial, statin therapy with bile acid resin decreased the incidence of coronary events by 70% despite producing only a 0.7% change in lesion regression.15,17 Indeed, many of the beneficial effects of statins in the FATS trial were attributed to plaque stabilization and remodeling. However, in the recent Myocardial Ischemia Reduction With Aggressive Cholesterol Lowering (MIRACL) trial, statins were found to be effective in reducing recurrent ischemic events as early as 16 weeks after acute coronary ischemia.18 Although the serum LDL cholesterol was reduced by 40%, this time frame was probably too short for appreciable changes in vascular remodeling. Therefore, it is believed that some other actions of statins, particularly the improvement of endothelial function, may have contributed to these early benefits (Table).19,20
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| Statins and Isoprenylated Proteins |
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subunit of heterotrimeric G proteins, Heme-a, nuclear lamins, and the small GTP-binding protein Ras and Ras-like proteins, such as Rho, Rab, Rac, Ral, and Rap.22 Thus, protein isoprenylation permits the covalent attachment, subcellular localization, and intracellular trafficking of membrane-associated proteins. Members of the Ras and Rho GTPase family are major substrates for posttranslational modification by prenylation.22,23 Ras and Rho are small GTP-binding proteins that cycle between the inactive GDP-bound state and active GTP-bound state. In endothelial cells, Ras translocation from the cytoplasm to the plasma membrane is dependent on farnesylation, whereas Rho translocation is dependent on geranylgeranylation.24,25 Statins inhibit Ras and Rho isoprenylation, leading to the accumulation of inactive Ras and Rho in the cytoplasm. .
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Because Rho is a major target of geranylgeranylation, inhibition of Rho and its downstream target, Rho kinase, is a likely mechanism mediating some of the pleiotropic effects of statins on the vascular wall.26 Each member of the Rho family serves specific functions in terms of cell shape, motility, secretion, and proliferation, although overlapping functions between the members could be observed in overexpressed systems. The activation of Rho in Swiss 3T3 fibroblasts by extracellular ligands, such as platelet-derived lysophosphatidic acid, leads to myosin light chain phosphorylation and the formation of focal adhesion complexes.22,23,27 Indeed, Rho-associated protein kinase increases the sensitivity of vascular smooth muscle to calcium in hypertension28 and coronary spasm.29 In contrast, activation of Rac leads to the formation of lamellipodia and membrane ruffles, whereas activation of Cdc42 induces actin-rich surface protrusions called filopodia. Thus, changes in Rho-induced actin cytoskeleton can affect intracellular transport, membrane trafficking, mRNA stability, and gene transcription. Indeed, evidence suggests that inhibition of Rho isoprenylation mediates many of the cholesterol-independent effects of statins not only in vascular wall cells24,30 but also in leukocytes31 and bone.32
| Statins and Endothelial Function |
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Acute plasma LDL apheresis improves endothelium-dependent vasodilatation,42 suggesting that statins could restore endothelial function, in part, by lowering serum cholesterol levels. However, in some studies with statins, restoration of endothelial function occurs before significant reduction in serum cholesterol levels,4345 suggesting that there may be additional effects on endothelial function beyond that of cholesterol reduction. Indeed, statins increase NO bioavailability by stimulating and upregulating endothelial NO synthase (eNOS)24,46 or by decreasing oxidative stress.47 Furthermore, statins have been shown to restore eNOS activity in the presence of hypoxia48 and oxidized LDL,24 conditions that lead to endothelial dysfunction. Statins also increase the expression of tissue-type plasminogen activator49 and inhibit the expression of endothelin-1, a potent vasoconstrictor and mitogen.50 Therefore, statins exert many favorable effects on the endothelium and attenuate endothelial dysfunction in the presence of atherosclerotic risk factors.
Whereas the effects of statins on Ras and Rho isoprenylation are reversed in the presence of FPP and GGPP, respectively, the effects of statins on eNOS expression are reversed only with GGPP and not with FPP or LDL cholesterol.25 These findings are consistent with a non-cholesterol-lowering effect of statins and suggest that inhibition of Rho by statins mediates the increase in eNOS expression (Figure 2). Indeed, statins upregulate eNOS expression by prolonging eNOS mRNA half-life but not eNOS gene transcription.25 Because hypoxia, oxidized LDL, and cytokines such as tumor necrosis factor-
decrease eNOS expression by reducing eNOS mRNA stability, the ability of statins to prolong eNOS half-life may make them effective agents in counteracting conditions that downregulate eNOS expression. .
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Another potential mechanism by which statins may improve endothelial function is through their antioxidant effects. For example, statins enhance endothelium-dependent relaxation by inhibiting the production of reactive oxygen species (ROS), such as such as superoxide and hydroxy radicals, from aortas of cholesterol-fed rabbits.47 Although lipid lowering by itself can lower vascular oxidative stress,51,52 some of these antioxidant effects of statins appear to be cholesterol independent. For example, statins attenuate angiotensin II-induced free radical production in vascular smooth muscle cells (SMCs) by inhibiting Rac1-mediated NADH oxidase activity and downregulating angiotensin type 1 receptor expression.53 Because NO is scavenged by ROS, these findings indicate that the antioxidant properties of statins may also contribute to their ability to improve endothelial function.40,41
| Statins and SMC Proliferation |
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Because the small GTP-binding proteins, Ras and Rho, require posttranslational modification for membrane localization and activity and are implicated in cell cycle regulation, they are likely targets for the direct antiproliferative vascular effects of statins. Ras can promote cell cycle progression via activation of the mitogen-activated protein kinase pathway,57 whereas Rho causes cellular proliferation possibly through destabilizing p27Kip1 protein.58 Interestingly, inhibition of vascular SMC proliferation by statins was reversed by GGPP, but not FPP or LDL cholesterol.30 Indeed, direct inhibition of Rho by Clostridium botulinum C3 transferase, which ADP-ribosylates and inactivates Rho, or by a dominant-negative Rho mutant increased p27Kip1 and inhibited Rb hyperphosphorylation and SMC proliferation after PDGF stimulation.30 Taken together, these findings indicate that Rho mediates PDGF-induced SMC proliferation and that inhibition of Rho by statins is the predominant mechanism by which statins inhibit vascular SMC proliferation.
| Statins and Platelet Function |
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2-adrenergic receptor density,66 and platelet cytosolic calcium.67 Statins have been shown to inhibit platelet function.6870 Potential mechanisms include a reduction in the production of thromboxane A2 and modifications in the cholesterol content of platelet membranes.71,72 The cholesterol content of platelet and erythrocyte membranes is reduced in patients undergoing statin therapy. This may lead to a decrease in the thrombogenic potential of these cells. Indeed, animal studies suggest that statin therapy inhibits platelet deposition on damaged vessels and reduces platelet thrombus formation.61,73,74 Furthermore, in vitro experiments have demonstrated that statins inhibit tissue factor expression by macrophages, thereby potentially reducing the thrombotic potential of the vascular wall.75
| Statins and Plaque Stability |
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Lipid lowering by statins may contribute to plaque stability by reducing plaque size or by modifying the physiochemical properties of the lipid core.86,87 However, as mentioned previously, changes in plaque size by lipid lowering tend to occur over extended time and are quite minimal, as assessed by angiography. Rather, the clinical benefits from lipid lowering are probably due to decreases in macrophage accumulation in atherosclerotic lesions and inhibition of MMP production by activated macrophages.75 Indeed, statins inhibit the expression of MMPs and tissue factor by cholesterol-dependent and -independent mechanisms,75,86,88 with the cholesterol-independent or direct macrophage effects occurring at a much earlier time frame. Therefore, the plaque-stabilizing properties of statins are mediated through a combined reduction in lipids, macrophages, and MMPs.89 These effects of statins may reduce the incidence of acute coronary syndromes by lessening the propensity for plaque to rupture.
| Statins and Vascular Inflammation |
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A clinical marker of inflammation is high-sensitivity C-reactive protein (hs-CRP).98 hs-CRP is an acute-phase reactant that is produced by the liver in response to proinflammatory cytokines, such as interleukin-6, and reflects low-grade systemic inflammation.99 Elevated levels of hs-CRP have been shown to be predictive of increased risk of coronary artery disease in apparently healthy men and women.36,100103 hs-CRP is elevated in patients with coronary artery disease, coronary ischemia, and myocardial infarction compared with normal subjects.43,104,105 Statin therapy lowers hs-CRP levels in hypercholesterolemic patients.98,106,107 In the CARE trial, statins significantly decreased plasma hs-CRP levels over a 5-year period in patients who did not experience recurrent coronary events.108,109 Similarly, an analysis of baseline and 1-year follow-up from the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) demonstrated that hs-CRP levels were reduced in statin-treated patients who were free of acute major coronary events.98 Therefore, these studies indicate that statins are effective in decreasing systemic and vascular inflammation. However, any potential clinical benefits conferred by the lowering of hs-CRP are difficult to separate from the benefits of the lipid-lowering effects of statins without performing further clinical studies.
| Statins and Ischemic Stroke |
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In addition to increases in cerebral blood flow, other beneficial effects of statins that have an impact on the severity of ischemic stroke are likely to occur. For example, statins attenuate P-selectin expression and leukocyte adhesion via increases in NO production in a model of cardiac ischemia and reperfusion.93,96 Others have reported that statins upregulate tissue-type plasminogen activator and downregulate plasminogen activator inhibitor-1 expression through a similar mechanism involving the inhibition of Rho geranylgeranylation.49 Thus, the absence of neuroprotection in eNOS-deficient mice emphasizes the importance of endothelium-derived NO not only in augmenting cerebral blood flow but also, potentially, in limiting the impact of platelet and white blood cell accumulation on tissue viability after ischemia. It is possible that statins may have contributed to the decrease in the incidence of ischemic strokes in clinical trials, in part, by reducing cerebral infarcts size to levels that are clinically unappreciated.
| Summary |
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| Acknowledgments |
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Received July 24, 2001; accepted August 29, 2001.
| References |
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2.
Gordon T, Kannel WB. Premature mortality from coronary heart disease: the Framingham study. JAMA. 1971; 215: 16171625.
3.
Kannel WB, Castelli WP, Gordon T, McNamara PM. Serum cholesterol, lipoproteins, and the risk of coronary heart disease: the Framingham study. Ann Intern Med. 1971; 74: 112.
4. Iso H, Jacobs DRJr, Wentworth D, Neaton JD, Cohen JD. Serum cholesterol levels and six-year mortality from stroke in 350,977 men screened for the multiple risk factor intervention trial. N Engl J Med. 1989; 320: 904910.[Abstract]
5. Sytkowski PA, Kannel WB, DAgostino RB. Changes in risk factors and the decline in mortality from cardiovascular disease: the Framingham Heart Study. N Engl J Med. 1990; 322: 16351641.[Abstract]
6. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994; 344: 13831389.[Medline] [Order article via Infotrieve]
7.
Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels: the Long-Term Intervention With Pravastatin in Ischaemic Disease (LIPID) Study Group. N Engl J Med. 1998; 339: 13491357.
8.
Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, Brown L, Warnica JW, Arnold JM, Wun CC, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels: Cholesterol and Recurrent Events Trial investigators. N Engl J Med. 1996; 335: 10011009.
9.
Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, McKillop JH, Packard CJ. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia: West of Scotland Coronary Prevention Study Group. N Engl J Med. 1995; 333: 13011307.
10.
Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, Langendorfer A,Stein EA, Kruyer W, Gotto AMJr. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS: Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA. 1998; 279: 16151622.
11. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993; 362: 801809.[Medline] [Order article via Infotrieve]
12.
Klag MJ, Ford DE, Mead LA, He J, Whelton PK, Liang KY, Levine DM. Serum cholesterol in young men and subsequent cardiovascular disease. N Engl J Med. 1993; 328: 313318.
13. Massy ZA, Keane WF, Kasiske BL. Inhibition of the mevalonate pathway: benefits beyond cholesterol reduction? Lancet. 1996; 347: 102103.[Medline] [Order article via Infotrieve]
14.
Packard CJ. Influence of pravastatin and plasma lipids on clinical events in the West of Scotland Coronary Prevention Study (WOSCOPS). Circulation. 1998; 97: 14401445.
15.
Brown BG, Zhao XQ, Sacco DE, Albers JJ. Lipid lowering and plaque regression: new insights into prevention of plaque disruption and clinical events in coronary disease. Circulation. 1993; 87: 17811791.
16. Pekkanen J, Linn S, Heiss G, Suchindran CM, Leon A, Rifkind BM, Tyroler HA. Ten-year mortality from cardiovascular disease in relation to cholesterol level among men with and without preexisting cardiovascular disease. N Engl J Med. 1990; 322: 17001707.[Abstract]
17. Brown BG, Hillger L, Zhao XQ, Poulin D, Albers JJ. Types of change in coronary stenosis severity and their relative importance in overall progression and regression of coronary disease: observations from the FATS Trial: Familial Atherosclerosis Treatment Study. Ann N Y Acad Sci. 1995; 748: 407418.[Medline] [Order article via Infotrieve]
18.
Schwartz GG, Olsson AG, Ezekowitz MD, Ganz P, Oliver MF, Waters D, Zeiher A, Chaitman BR, Leslie S, Stern T. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA. 2001; 285: 17111718.
19. Bellosta S, Ferri N, Bernini F, Paoletti R, Corsini A. Non-lipid-related effects of statins. Ann Med. 2000; 32: 164176.[Medline] [Order article via Infotrieve]
20. Bellosta S, Ferri N, Arnaboldi L, Bernini F, Paoletti R, Corsini A. Pleiotropic effects of statins in atherosclerosis and diabetes. Diabetes Care. 2000; 23 (suppl 2): B72B78.[Medline] [Order article via Infotrieve]
21. Goldstein JL, Brown MS. Regulation of the mevalonate pathway. Nature. 1990; 343: 425430.[Medline] [Order article via Infotrieve]
22.
Van Aelst L, D Souza-Schorey C. Rho GTPases and signaling networks. Genes Dev. 1997; 11: 22952322.
23.
Hall A. Rho GTPases and the actin cytoskeleton. Science. 1998; 279: 509514.
24.
Laufs U, La Fata V, Plutzky J, Liao JK. Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation. 1998; 97: 11291135.
25.
Laufs U, Liao JK. Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by Rho GTPase. J Biol Chem. 1998; 273: 2426624271.
26. Laufs U, Endres M, Stagliano N, Amin-Hanjani S, Chui DS, Yang SX, Simoncini T, Yamada M, Rabkin E, Allen PG, et al. Neuroprotection mediated by changes in the endothelial actin cytoskeleton. J Clin Invest. 2000; 106: 1524.[Medline] [Order article via Infotrieve]
27. Hall A, Small GTP-binding proteins and the regulation of the actin cytoskeleton. Annu Rev Cell Biol. 1994; 10: 3154.
28. Uehata M, Ishizaki T, Satoh H, Ono T, Kawahara T, Morishita T, Tamakawa H, Yamagami K, Inui J, Maekawa M, et al. Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature. 1997; 389: 990994.[Medline] [Order article via Infotrieve]
29.
Katsumata N, Shimokawa H, Seto M, Kozai T, Yamawaki T, Kuwata K, Egashira K, Ikegaki I, Asano T, Sasaki Y, et al. Enhanced myosin light chain phosphorylations as a central mechanism for coronary artery spasm in a swine model with interleukin-1beta. Circulation. 1997; 96: 43574363.
30.
Laufs U, Marra D, Node K, Liao JK. 3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors attenuate vascular smooth muscle proliferation by preventing rho GTPase-induced down- regulation of p27(Kip1). J Biol Chem. 1999; 274: 2192621931.
31. Singh R, Wang B, Shirvaikar A, Khan S, Kamat S, Schelling JR, Konieczkowski M, Sedor JR. The IL-1 receptor and Rho directly associate to drive cell activation in inflammation. J Clin Invest. 1999; 103: 15611570.[Medline] [Order article via Infotrieve]
32.
Mundy G, Garrett R, Harris S, Chan J, Chen D, Rossini G, Boyce B, Zhao M, Gutierrez G. Stimulation of bone formation in vitro and in rodents by statins. Science. 1999; 286: 19461949.
33.
Liao JK, Bettmann MA, Sandor T, Tucker JI, Coleman SM, Creager MA. Differential impairment of vasodilator responsiveness of peripheral resistance and conduit vessels in humans with atherosclerosis. Circ Res. 1991; 68: 10271034.
34. Libby P, Sukhova G, Lee RT, Liao JK. Molecular biology of atherosclerosis. Int J Cardiol. 1997; 62 (suppl 2): S23S29.
35.
Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci U S A. 1987; 84: 92659269.
36. Radomski MW, Rees DD, Dutra A, Moncada S. S-Nitroso-glutathione inhibits platelet activation in vitro and in vivo. Br J Pharmacol. 1992; 107: 745749.[Medline] [Order article via Infotrieve]
37. 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: 17741777.[Medline] [Order article via Infotrieve]
38.
Gauthier TW, Scalia R, Murohara T, Guo JP, Lefer AM. Nitric oxide protects against leukocyte-endothelium interactions in the early stages of hypercholesterolemia. Arterioscler Thromb Vasc Biol. 1995; 15: 16521659.
39.
Kubes P, Suzuki M, Granger DN. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci U S A. 1991; 88: 46514655.
40. Harrison DG. Cellular and molecular mechanisms of endothelial cell dysfunction. J Clin Invest. 1997; 100: 21532157.[Medline] [Order article via Infotrieve]
41. Munzel T, Sayegh H, Freeman BA, Tarpey MM, Harrison DG. Evidence for enhanced vascular superoxide anion production in nitrate tolerance: a novel mechanism underlying tolerance and cross-tolerance. J Clin Invest. 1995; 95: 187194.[Medline] [Order article via Infotrieve]
42.
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: 7682.
43.
Anderson TJ, Meredith IT, Yeung AC, Frei B, Selwyn AP, Ganz P. The effect of cholesterol-lowering and antioxidant therapy on endothelium-dependent coronary vasomotion. N Engl J Med. 1995; 332: 488493.
44.
O Driscoll G, Green D, Taylor RR. Simvastatin, an HMG-coenzyme: a reductase inhibitor, improves endothelial function within 1 month. Circulation. 1997; 95: 11261131.
45.
Treasure CB, Klein JL, Weintraub WS, Talley JD, Stillabower ME, Kosinski AS, Zhang J, Boccuzzi SJ, Cedarholm JC, Alexander RW. Beneficial effects of cholesterol-lowering therapy on the coronary endothelium in patients with coronary artery disease. N Engl J Med. 1995; 332: 481487.
46. Kureishi Y, Luo Z, Shiojima I, Bialik A, Fulton D, Lefer DJ, Sessa WC,Walsh K. The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nat Med. 2000; 6: 10041010.[Medline] [Order article via Infotrieve]
47. Rikitake Y, Kawashima S, Takeshita S, Yamashita T, Azumi H, Yasuhara M, Nishi H, Inoue N, Yokoyama M. Anti-oxidative properties of fluvastatin, an HMG-CoA reductase inhibitor, contribute to prevention of atherosclerosis in cholesterol-fed rabbits. Atherosclerosis. 2001; 154: 8796.[Medline] [Order article via Infotrieve]
48.
Laufs U, Fata VL, 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: 3172531729.
49.
Essig M, Nguyen G, Prie D, Escoubet B, Sraer JD, Friedlander G. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors increase fibrinolytic activity in rat aortic endothelial cells: role of geranylgeranylation and Rho proteins. Circ Res. 1998; 83: 683690.
50. 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: 27112719.[Medline] [Order article via Infotrieve]
51.
Cai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res. 2000; 87: 840844.
52. Landmesser U, Hornig B, Drexler H. Endothelial dysfunction in hypercholesterolemia: mechanisms, pathophysiological importance, and therapeutic interventions. Semin Thromb Hemost. 2000; 26: 529537.[Medline] [Order article via Infotrieve]
53.
Wassmann S, Laufs U, Baumer AT, Muller K, Ahlbory K, Linz W, Itter G, Rosen R, Bohm M, Nickenig G. HMG-CoA reductase inhibitors improve endothelial dysfunction in normocholesterolemic hypertension via reduced production of reactive oxygen species. Hypertension. 2001; 37: 14501457.
54.
Braun-Dullaeus RC, Mann MJ, Dzau VJ. Cell cycle progression: new therapeutic target for vascular proliferative disease. Circulation. 1998; 98: 8289.
55.
Kobashigawa JA, Katznelson S, Laks H, Johnson JA, Yeatman L, Wang XM, Chia D, Terasaki PI, Sabad A, Cogert GA, et al. Effect of pravastatin on outcomes after cardiac transplantation. N Engl J Med. 1995; 333: 621627.
56.
Yang Z, Kozai T, van der Loo B, Viswambharan H, Lachat M, Turina MI, Malinski T, Luscher TF. HMG-CoA reductase inhibition improves endothelial cell function and inhibits smooth muscle cell proliferation in human saphenous veins. J Am Coll Cardiol. 2000; 36: 16911697.
57. Hughes DA. Control of signal transduction and morphogenesis by Ras. Semin Cell Biol. 1995; 6: 8994.[Medline] [Order article via Infotrieve]
58. Hengst L, Reed SI. Translational control of p27Kip1 accumulation during the cell cycle. Science. 1996; 271: 18611864.[Abstract]
59. Fitzgerald DJ, Roy L, Catella F, FitzGerald GA. Platelet activation in unstable coronary disease. N Engl J Med. 1986; 315: 983989.[Abstract]
60. Fuster V, Badimon JJ, Badimon L. Clinical-pathological correlations of coronary disease progression and regression. Circulation. 1992; 86 (suppl III): III-1III-11.
61.
Lacoste L, Lam JY, Hung J, Letchacovski G, Solymoss CB, Waters D. Hyperlipidemia and coronary disease: correction of the increased thrombogenic potential with cholesterol reduction. Circulation. 1995; 92: 31723177.
62.
Willerson JT, Golino P, Eidt J, Campbell WB, Buja LM. Specific platelet mediators and unstable coronary artery lesions: experimental evidence and potential clinical implications. Circulation. 1989; 80: 198205.
63. Opper C, Clement C, Schwarz H, Krappe J, Steinmetz A, Schneider J, Wesemann W. Increased number of high sensitive platelets in hypercholesterolemia, cardiovascular diseases, and after incubation with cholesterol. Atherosclerosis. 1995; 113: 211217.[Medline] [Order article via Infotrieve]
64. Tremoli E, Colli S, Maderna P, Baldassarre D, Di Minno G. Hypercholesterolemia and platelets. Semin Thromb Hemost. 1993; 19: 115121.[Medline] [Order article via Infotrieve]
65.
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: 247251.
66. Baldassarre D, Mores N, Colli S, Pazzucconi F, Sirtori CR, Tremoli E. Platelet alpha 2-adrenergic receptors in hypercholesterolemia: relationship between binding studies and epinephrine-induced platelet aggregation. Clin Pharmacol Ther. 1997; 61: 684691.[Medline] [Order article via Infotrieve]
67.
Le Quan Sang KH, Levenson J, Megnien JL, Simon A, Devynck MA. Platelet cytosolic Ca2+ and membrane dynamics in patients with primary hypercholesterolemia: effects of pravastatin. Arterioscler Thromb Vasc Biol. 1995; 15: 759764.
68. 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: 229234.[Medline] [Order article via Infotrieve]
69.
Hale LP, Craver KT, Berrier AM, Sheffield MV, Case LD, Owen J. Combination of fosinopril and pravastatin decreases platelet response to thrombin receptor agonist in monkeys. Arterioscler Thromb Vasc Biol. 1998; 18: 16431646.
70. Schror K. Platelet reactivity and arachidonic acid metabolism in type II hyperlipoproteinaemia and its modification by cholesterol-lowering agents. Eicosanoids. 1990; 3: 6773.[Medline] [Order article via Infotrieve]
71.
Vaughan CJ, Gotto AMJr, Basson CT. The evolving role of statins in the management of atherosclerosis. J Am Coll Cardiol. 2000; 35: 110.
72. Lijnen P, Echevaria-Vazquez D, Petrov V. Influence of cholesterol-lowering on plasma membrane lipids and function. Methods Find Exp Clin Pharmacol. 1996; 18: 123136.[Medline] [Order article via Infotrieve]
73.
Alfon J, Royo T, Garcia-Moll X, Badimon L. Platelet deposition on eroded vessel walls at a stenotic shear rate is inhibited by lipid-lowering treatment with atorvastatin. Arterioscler Thromb Vasc Biol. 1999; 19: 18121817.
74. Alfon J, Fernandez de Arriba A, Gomez-Casajus LA, Merlos M. Alternative binding assay of gp iib/iiia antagonists with a nonradioactive labeling method of platelets. Thromb Res. 2001; 102: 247253.[Medline] [Order article via Infotrieve]
75.
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: 276283.
76. Fuster V. Elucidation of the role of plaque instability and rupture in acute coronary events. Am J Cardiol. 1995; 76: 24C33C.[Medline] [Order article via Infotrieve]
77. Chesebro JH, Zoldhelyi P, Fuster V. Pathogenesis of thrombosis in unstable angina. Am J Cardiol. 1991; 68: 2B10B.[Medline] [Order article via Infotrieve]
78. Fuster V, Stein B, Ambrose JA, Badimon L, Badimon JJ, Chesebro JH. Atherosclerotic plaque rupture and thrombosis: evolving concepts. Circulation. 1990; 82 (suppl II): II-47II-59.[Medline] [Order article via Infotrieve]
79.
Libby P. Molecular bases of the acute coronary syndromes. Circulation. 1995; 91: 28442850.
80. Fernandez-Ortiz A, Badimon JJ, Falk E, Fuster V, Meyer B, Mailhac A, Weng D, Shah PK, Badimon L. Characterization of the relative thrombogenicity of atherosclerotic plaque components: implications for consequences of plaque rupture. J Am Coll Cardiol. 1994; 23: 15621569.[Abstract]
81.
Moreno PR, Falk E, Palacios IF, Newell JB, Fuster V, Fallon JT. Macrophage infiltration in acute coronary syndromes: implications for plaque rupture. Circulation. 1994; 90: 775778.
82. Shah PK, Falk E, Badimon JJ, Fernandez-Ortiz A, Mailhac A, Villareal-Levy G, Fallon JT, Regnstrom J, Fuster V. 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: 15651569.[Medline] [Order article via Infotrieve]
83.
Henney AM, Wakeley PR, Davies MJ, Foster K, Hembry R, Murphy G, Humphries S. Localization of stromelysin gene expression in atherosclerotic plaques by in situ hybridization. Proc Natl Acad Sci U S A. 1991; 88: 81548158.
84. Richardson PD, Davies MJ, Born GV. Influence of plaque configuration and stress distribution on fissuring of coronary atherosclerotic plaques. Lancet. 1989; 2: 941944.[Medline] [Order article via Infotrieve]
85.
Davies MJ. Acute coronary thrombosis: the role of plaque disruption and its initiation and prevention. Eur Heart J. 1995; 16 (suppl L): 37.
86.
Fukumoto Y, Libby P, Rabkin E, Hill CC, Enomoto M, Hirouchi Y, Shiomi M, Aikawa M. Statins alter smooth muscle cell accumulation and collagen content in established atheroma of Watanabe heritable hyperlipidemic rabbits. Circulation. 2001; 103: 993999.
87.
Koh KK. Effects of statins on vascular wall: vasomotor function, inflammation, and plaque stability. Cardiovasc Res. 2000; 47: 648657.
88.
Bourcier T, Libby P. HMG CoA reductase inhibitors reduce plasminogen activator inhibitor-1 expression by human vascular smooth muscle and endothelial cells. Arterioscler Thromb Vasc Biol. 2000; 20: 556562.
89.
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: 926933.
90. Ross R. Atherosclerosis is an inflammatory disease. Am Heart J. 1999; 138: S419S420.[Medline] [Order article via Infotrieve]
91. Niwa S, Totsuka T, Hayashi S. Inhibitory effect of fluvastatin, an HMG-CoA reductase inhibitor, on the expression of adhesion molecules on human monocyte cell line. Int J Immunopharmacol. 1996; 18: 669675.[Medline] [Order article via Infotrieve]
92. 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: 687692.[Medline] [Order article via Infotrieve]
93.
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: 178184.
94.
Scalia R, Gooszen ME, Jones SP, Hoffmeyer M, Rimmer DMIII, Trocha SD, Huang PL, Smith MB, Lefer AM, Lefer DJ. Simvastatin exerts both anti-inflammatory and cardioprotective effects in apolipoprotein e-deficient mice. Circulation. 2001; 103: 25982603.
95.
Lefer DJ, Scalia R, Jones SP, Sharp BR, Hoffmeyer MR, Farvid AR, Gibson MF, Lefer AM. HMG-CoA reductase inhibition protects the diabetic myocardium from ischemia-reperfusion injury. FASEB J. 2001; 15: 14541456.
96.
Lefer AM, Scalia R, Lefer DJ. Vascular effects of HMG CoA-reductase inhibitors (statins) unrelated to cholesterol lowering: new concepts for cardiovascular disease. Cardiovasc Res. 2001; 49: 281287.
97. Stalker TJ, Lefer AM, Scalia R. A new HMG-CoA reductase inhibitor, rosuvastatin, exerts anti-inflammatory effects on the microvascular endothelium: the role of mevalonic acid. Br J Pharmacol. 2001; 133: 406412.[Medline] [Order article via Infotrieve]
98.
Ridker PM, Rifai N, Clearfield M, Downs JR, Weis SE, Miles JS, Gotto AMJr. 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: 19591965.
99. Baumann H, Gauldie J. The acute phase response. Immunol Today. 1994; 15: 7480.[Medline] [Order article via Infotrieve]
100.
Koenig W, Sund M, Frohlich M, Fischer HG, Lowel H, Doring A, Hutchinson WL, Pepys MB. C-reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992. Circulation. 1999; 99: 237242.
101.
Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997; 336: 973979.
102.
Ridker PM, Buring JE, Shih J, Matias M, Hennekens CH. Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation. 1998; 98: 731733.
103.
Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000; 342: 836843.
104.
Liuzzo G, Biasucci LM, Gallimore JR, Grillo RL, Rebuzzi AG, Pepys MB, Maseri A. The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. N Engl J Med. 1994; 331: 417424.
105.
Mendall MA, Patel P, Ballam L, Strachan D, Northfield TC. C reactive protein and its relation to cardiovascular risk factors: a population based cross sectional study. BMJ. 1996; 312: 10611065.
106. Musial J, Undas A, Gajewski P, Jankowski M, Sydor W, Szczeklik A. Anti-inflammatory effects of simvastatin in subjects with hypercholesterolemia. Int J Cardiol. 2001; 77: 247253.[Medline] [Order article via Infotrieve]
107.
Ridker PM, Rifai N, Lowenthal SP. Rapid reduction in C-reactive protein with cerivastatin among 785 patients with primary hypercholesterolemia. Circulation. 2001; 103: 11911193.
108.
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: 230235.
109.
Ridker PM, Rifai N, Pfeffer MA, Sacks FM, Moye LA, Goldman S, Flaker GC, Braunwald E. Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels: Cholesterol and Recurrent Events (CARE) Investigators. Circulation. 1998; 98: 839844.
110. Crouse JR, Byington RP, Furberg CD. HMG-CoA reductase inhibitor therapy and stroke risk reduction: an analysis of clinical trials data. Atherosclerosis. 1998; 138: 1124.[Medline] [Order article via Infotrieve]
111.
Multiple risk factor intervention trial: risk factor changes and mortality results: Multiple Risk Factor Intervention Trial Research Group. JAMA. 1982; 248: 14651477.
112.
Endres M, Laufs U, Huang Z, Nakamura T, Huang P, Moskowitz MA, Liao JK. Stroke protection by 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors mediated by endothelial nitric oxide synthase. Proc Natl Acad Sci U S A. 1998; 95: 88808885.
113. Inoue I, Goto S, Mizotani K, Awata T, Mastunaga T, Kawai S, Nakajima T, Hokari S, Komoda T, Katayama S. Lipophilic HMG-CoA reductase inhibitor has an anti-inflammatory effect: reduction of MRNA levels for interleukin-1beta, interleukin-6, cyclooxygenase-2, and p22phox by regulation of peroxisome proliferator-activated receptor alpha (PPARalpha) in primary endothelial cells. Life Sci. 2000; 67: 863876.[Medline] [Order article via Infotrieve]
114. Kwak B, Mulhaupt F, Myit S, Mach F. Statins as a newly recognized type of immunomodulator. Nat Med. 2000; 6: 13991402.[Medline] [Order article via Infotrieve]
115.
Wassmann S, Laufs U, Baumer AT, Muller K, Konkol C, Sauer H, Bohm M, Nickenig G. Inhibition of geranylgeranylation reduces angiotensin II-mediated free radical production in vascular smooth muscle cells: involvement of angiotensin AT1 receptor expression and Rac1 GTPase. Mol Pharmacol. 2001; 59: 646654.
116.
Guijarro C, Blanco-Colio LM, Ortego M, Alonso C, Ortiz A, Plaza JJ, Diaz C, Hernandez G, Edigo J. 3-Hydroxy-3-methylglutaryl coenzyme a reductase and isoprenylation inhibitors induce apoptosis of vascular smooth muscle cells in culture. Circ Res. 1998; 83: 490500.
117. Sakai M, Kobori S, Matsumura T, Biwa T, Sato Y, Takemura T, Hakamata H, Horiuchi S, Shichiri M. HMG-CoA reductase inhibitors suppress macrophage growth induced by oxidized low density lipoprotein. Atherosclerosis. 1997; 133: 5159.[Medline] [Order article via Infotrieve]
118. Pahan K, Sheikh FG, Namboodiri AM, Singh I. Lovastatin and phenylacetate inhibit the induction of nitric oxide synthase and cytokines in rat primary astrocytes, microglia, and macrophages. J Clin Invest. 1997; 100: 26712679.[Medline] [Order article via Infotrieve]
119.
Kothe H, Dalhoff K, Rupp J, Muller A, Kreuzer J, Maass M, Katus HA. Hydroxymethylglutaryl coenzyme: a reductase inhibitors modify the inflammatory response of human macrophages and endothelial cells infected with Chlamydia pneumoniae. Circulation. 2000; 101: 17601763.
120.
Gauthier TW, Scalia R, Murohara T, Guo JP, Lefer AM. Nitric oxide protects against leukocyte-endothelium interactions in the early stages of hypercholesterolemia. Artherioscler Thromb Vasc Biol. 1995; 15: 16521659.
121.
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: 20572064.
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N. Tanaka, Y. Momiyama, R. Ohmori, A. Yonemura, M. Ayaori, M. Ogura, S. Sawada, M. Kusuhara, H. Nakamura, and F. Ohsuzu Effect of atorvastatin on plasma osteopontin levels in patients with hypercholesterolemia. Arterioscler Thromb Vasc Biol, August 1, 2006; 26(8): e129 - e130. [Full Text] [PDF] |
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K. Groschel, U. Ernemann, J. B. Schulz, T. Nagele, C. Terborg, and A. Kastrup Statin Therapy at Carotid Angioplasty and Stent Placement: Effect on Procedure-related Stroke, Myocardial Infarction, and Death. Radiology, July 1, 2006; 240(1): 145 - 151. [Abstract] [Full Text] [PDF] |
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K. Sakoda, M. Yamamoto, Y. Negishi, J.K. Liao, K. Node, and Y. Izumi Simvastatin Decreases IL-6 and IL-8 Production in Epithelial Cells Journal of Dental Research, June 1, 2006; 85(6): 520 - 523. [Abstract] [Full Text] [PDF] |
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M. Ohkita, M. Sugii, Y. Ka, A. Kitamura, T. Mori, T. Hayashi, M. Takaoka, and Y. Matsumura Differential Effects of Different Statins on Endothelin-1 Gene Expression and Endothelial NOS Phosphorylation in Porcine Aortic Endothelial Cells. Experimental Biology and Medicine, June 1, 2006; 231(6): 772 - 776. [Abstract] [Full Text] [PDF] |
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J. J. Maguire, K. E. Wiley, R. E. Kuc, V. E. A. Stoneman, M. R. Bennett, and A. P. Davenport Endothelin-Mediated Vasoconstriction in Early Atherosclerosis Is Markedly Increased in ApoE-/- Mouse but Prevented by Atorvastatin. Experimental Biology and Medicine, June 1, 2006; 231(6): 806 - 812. [Abstract] [Full Text] [PDF] |
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H. Bujo and Y. Saito Modulation of Smooth Muscle Cell Migration by Members of the Low-Density Lipoprotein Receptor Family Arterioscler Thromb Vasc Biol, June 1, 2006; 26(6): 1246 - 1252. [Abstract] [Full Text] [PDF] |
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M. Arora, L. Chen, M. Paglia, I. Gallagher, J. E. Allen, Y. M. Vyas, A. Ray, and P. Ray Simvastatin promotes Th2-type responses through the induction of the chitinase family member Ym1 in dendritic cells PNAS, May 16, 2006; 103(20): 7777 - 7782. [Abstract] [Full Text] [PDF] |
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V. Liebe, M. Brueckmann, M. Borggrefe, and J. J. Kaden Statin therapy of calcific aortic stenosis: hype or hope? Eur. Heart J., April 1, 2006; 27(7): 773 - 778. [Abstract] [Full Text] [PDF] |
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J. Segura, J. A. Garcia-Donaire, M. Praga, and L. M. Ruilope Chronic Kidney Disease as a Situation of High Added Risk in Hypertensive Patients J. Am. Soc. Nephrol., April 1, 2006; 17(4_suppl_2): S136 - S140. [Abstract] [Full Text] [PDF] |
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G. D'Amico Statins and Renal Diseases: From Primary Prevention to Renal Replacement Therapy. J. Am. Soc. Nephrol., April 1, 2006; 17(4_suppl_2): S148 - S152. [Abstract] [Full Text] [PDF] |
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S. Shibata, M. Nagase, and T. Fujita Fluvastatin Ameliorates Podocyte Injury in Proteinuric Rats via Modulation of Excessive Rho Signaling J. Am. Soc. Nephrol., March 1, 2006; 17(3): 754 - 764. [Abstract] [Full Text] [PDF] |
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G. Loirand, P. Guerin, and P. Pacaud Rho Kinases in Cardiovascular Physiology and Pathophysiology Circ. Res., February 17, 2006; 98(3): 322 - 334. [Abstract] [Full Text] [PDF] |
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R. Paumelle, C. Blanquart, O. Briand, O. Barbier, C. Duhem, G. Woerly, F. Percevault, J.-C. Fruchart, D. Dombrowicz, C. Glineur, et al. Acute Antiinflammatory Properties of Statins Involve Peroxisome Proliferator-Activated Receptor-{alpha} via Inhibition of the Protein Kinase C Signaling Pathway Circ. Res., February 17, 2006; 98(3): 361 - 369. [Abstract] [Full Text] [PDF] |
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M. J. Haas, M. H. Horani, S. A. Parseghian, and A. D. Mooradian Statins Prevent Dextrose-Induced Endothelial Barrier Dysfunction, Possibly Through Inhibition of Superoxide Formation Diabetes, February 1, 2006; 55(2): 474 - 479. [Abstract] [Full Text] [PDF] |
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P. Amarenco and M. A. Moskowitz The Dynamics of Statins: From Event Prevention to Neuroprotection Stroke, February 1, 2006; 37(2): 294 - 296. [Full Text] [PDF] |
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D. A. Pascual, J. M. Arribas, P. L. Tornel, F. Marin, C. Oliver, M. Ahumada, J. Gomez-Plana, P. Martinez, R. Arcas, and M. Valdes Preoperative Statin Therapy and Troponin T Predict Early Complications of Coronary Artery Surgery Ann. Thorac. Surg., January 1, 2006; 81(1): 78 - 83. [Abstract] [Full Text] [PDF] |
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D. Hartung, M. Sarai, A. Petrov, F. Kolodgie, N. Narula, J. Verjans, R. Virmani, C. Reutelingsperger, L. Hofstra, and J. Narula Resolution of Apoptosis in Atherosclerotic Plaque by Dietary Modification and Statin Therapy J. Nucl. Med., December 1, 2005; 46(12): 2051 - 2056. [Abstract] [Full Text] [PDF] |
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S. Van Doornum, G. McColl, and I. P. Wicks Tumour necrosis factor antagonists improve disease activity but not arterial stiffness in rheumatoid arthritis Rheumatology, November 1, 2005; 44(11): 1428 - 1432. [Abstract] [Full Text] [PDF] |
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A. D. Mooradian, M. J. Haas, O. Batejko, M. Hovsepyan, and S. S. Feman Statins Ameliorate Endothelial Barrier Permeability Changes in the Cerebral Tissue of Streptozotocin-Induced Diabetic Rats Diabetes, October 1, 2005; 54(10): 2977 - 2982. [Abstract] [Full Text] [PDF] |
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H. Shimokawa and A. Takeshita Rho-Kinase Is an Important Therapeutic Target in Cardiovascular Medicine Arterioscler Thromb Vasc Biol, September 1, 2005; 25(9): 1767 - 1775. [Abstract] [Full Text] [PDF] |
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A. Jula, J. Marniemi, T. Ronnemaa, A. Virtanen, and R. Huupponen Effects of Diet and Simvastatin on Fatty Acid Composition in Hypercholesterolemic Men: A Randomized Controlled Trial Arterioscler Thromb Vasc Biol, September 1, 2005; 25(9): 1952 - 1959. [Abstract] [Full Text] [PDF] |
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J. Shannon, S. Tewoderos, M. Garzotto, T. M. Beer, R. Derenick, A. Palma, and P. E. Farris Statins and Prostate Cancer Risk: A Case-Control Study Am. J. Epidemiol., August 15, 2005; 162(4): 318 - 325. [Abstract] [Full Text] [PDF] |
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M.-Y. Tseng, M. Czosnyka, H. Richards, J. D. Pickard, and P. J. Kirkpatrick Effects of Acute Treatment With Pravastatin on Cerebral Vasospasm, Autoregulation, and Delayed Ischemic Deficits After Aneurysmal Subarachnoid Hemorrhage: A Phase II Randomized Placebo-Controlled Trial Stroke, August 1, 2005; 36(8): 1627 - 1632. [Abstract] [Full Text] [PDF] |
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R. Corti, V. Fuster, Z. A. Fayad, S. G. Worthley, G. Helft, W. F. Chaplin, J. Muntwyler, J. F. Viles-Gonzalez, J. Weinberger, D. A. Smith, et al. Effects of Aggressive Versus Conventional Lipid-Lowering Therapy by Simvastatin on Human Atherosclerotic Lesions: A Prospective, Randomized, Double-Blind Trial With High-Resolution Magnetic Resonance Imaging J. Am. Coll. Cardiol., July 5, 2005; 46(1): 106 - 112. [Abstract] [Full Text] [PDF] |
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H. Methe, J.-O. Kim, S. Kofler, M. Nabauer, and M. Weis Statins Decrease Toll-Like Receptor 4 Expression and Downstream Signaling in Human CD14+ Monocytes Arterioscler Thromb Vasc Biol, July 1, 2005; 25(7): 1439 - 1445. [Abstract] [Full Text] [PDF] |
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C. A. Argmann, J. Y. Edwards, C. G. Sawyez, C. H. O'Neil, R. A. Hegele, J. G. Pickering, and M. W. Huff Regulation of Macrophage Cholesterol Efflux through Hydroxymethylglutaryl-CoA Reductase Inhibition: A ROLE FOR RhoA IN ABCA1-MEDIATED CHOLESTEROL EFFLUX J. Biol. Chem., June 10, 2005; 280(23): 22212 - 22221. [Abstract] [Full Text] [PDF] |
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M. Yamakuchi, J. J.M. Greer, S. J. Cameron, K. Matsushita, C. N. Morrell, K. Talbot-Fox, W. M. Baldwin III, D. J. Lefer, and C. J. Lowenstein HMG-CoA Reductase Inhibitors Inhibit Endothelial Exocytosis and Decrease Myocardial Infarct Size Circ. Res., June 10, 2005; 96(11): 1185 - 1192. [Abstract] [Full Text] [PDF] |
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H. Lorenz, C. Junger, K. Seidl, A. Gitt, S. Schneider, R. Schiele, H. Wienbergen, R. Winkler, M. Gottwik, W. Delius, et al. Do statins influence the prognostic impact of non-sustained ventricular tachycardia after ST-elevation myocardial infarction? Eur. Heart J., June 1, 2005; 26(11): 1078 - 1085. [Abstract] [Full Text] [PDF] |
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R. Sugano, H. Matsuoka, N. Haramaki, H. Umei, E. Murase, K. Fukami, S. Iida, H. Ikeda, and T. Imaizumi Polymorphonuclear Leukocytes May Impair Endothelial Function: Results of Crossover Randomized Study of Lipid-Lowering Therapies Arterioscler Thromb Vasc Biol, June 1, 2005; 25(6): 1262 - 1267. [Abstract] [Full Text] [PDF] |
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A. D. Mooradian Commentary J. Gerontol. A Biol. Sci. Med. Sci., May 1, 2005; 60(5): 598 - 598. [Full Text] [PDF] |
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L. H. Smith, M. S. Petrie, J. D. Morrow, J. A. Oates, and D. E. Vaughan The sterol response element binding protein regulates cyclooxygenase-2 gene expression in endothelial cells J. Lipid Res., May 1, 2005; 46(5): 862 - 871. [Abstract] [Full Text] [PDF] |
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Y. Urano, I. Hayashi, N. Isoo, P. C. Reid, Y. Shibasaki, N. Noguchi, T. Tomita, T. Iwatsubo, T. Hamakubo, and T. Kodama Association of active {gamma}-secretase complex with lipid rafts J. Lipid Res., May 1, 2005; 46(5): 904 - 912. [Abstract] [Full Text] [PDF] |
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A. G. Olsson, G. G. Schwartz, M. Szarek, W. J. Sasiela, M. D. Ezekowitz, P. Ganz, M. F. Oliver, D. Waters, and A. Zeiher High-density lipoprotein, but not low-density lipoprotein cholesterol levels influence short-term prognosis after acute coronary syndrome: results from the MIRACL trial Eur. Heart J., May 1, 2005; 26(9): 890 - 896. [Abstract] [Full Text] [PDF] |
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S. J. Zieman, V. Melenovsky, and D. A. Kass Mechanisms, Pathophysiology, and Therapy of Arterial Stiffness Arterioscler Thromb Vasc Biol, May 1, 2005; 25(5): 932 - 943. [Abstract] [Full Text] [PDF] |
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A. Schafer, D. Fraccarollo, M. Eigenthaler, P. Tas, A. Firnschild, S. Frantz, G. Ertl, and J. Bauersachs Rosuvastatin Reduces Platelet Activation in Heart Failure: Role of NO Bioavailability Arterioscler Thromb Vasc Biol, May 1, 2005; 25(5): 1071 - 1077. [Abstract] [Full Text] [PDF] |
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G. K. Hansson Inflammation, Atherosclerosis, and Coronary Artery Disease N. Engl. J. Med., April 21, 2005; 352(16): 1685 - 1695. [Full Text] [PDF] |
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S. Steiner, W. S. Speidl, J. Pleiner, D. Seidinger, G. Zorn, C. Kaun, J. Wojta, K. Huber, E. Minar, M. Wolzt, et al. Simvastatin Blunts Endotoxin-Induced Tissue Factor In Vivo Circulation, April 12, 2005; 111(14): 1841 - 1846. [Abstract] [Full Text] [PDF] |
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R. Madonna, P. Di Napoli, M. Massaro, A. Grilli, M. Felaco, A. De Caterina, D. Tang, R. De Caterina, and Y.-J. Geng Simvastatin Attenuates Expression of Cytokine-inducible Nitric-oxide Synthase in Embryonic Cardiac Myoblasts J. Biol. Chem., April 8, 2005; 280(14): 13503 - 13511. [Abstract] [Full Text] [PDF] |
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L. Sironi, E. Gianazza, P. Gelosa, U. Guerrini, E. Nobili, A. Gianella, B. Cremonesi, R. Paoletti, and E. Tremoli Rosuvastatin, but not Simvastatin, Provides End-Organ Protection in Stroke-Prone Rats by Antiinflammatory Effects Arterioscler Thromb Vasc Biol, March 1, 2005; 25(3): 598 - 603. [Abstract] [Full Text] [PDF] |
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M. Fu, J. Zhang, Y.-H. Tseng, T. Cui, X. Zhu, Y. Xiao, Y. Mou, H. De Leon, M. M.J. Chang, Y. Hamamori, et al. Rad GTPase Attenuates Vascular Lesion Formation by Inhibition of Vascular Smooth Muscle Cell Migration Circulation, March 1, 2005; 111(8): 1071 - 1077. [Abstract] [Full Text] [PDF] |
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T. Senokuchi, T. Matsumura, M. Sakai, M. Yano, T. Taguchi, T. Matsuo, K. Sonoda, D. Kukidome, K. Imoto, T. Nishikawa, et al. Statins Suppress Oxidized Low Density Lipoprotein-induced Macrophage Proliferation by Inactivation of the Small G Protein-p38 MAPK Pathway J. Biol. Chem., February 25, 2005; 280(8): 6627 - 6633. [Abstract] [Full Text] [PDF] |
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A. Undas, K. E. Brummel-Ziedins, and K. G. Mann Statins and Blood Coagulation Arterioscler Thromb Vasc Biol, February 1, 2005; 25(2): 287 - 294. [Abstract] [Full Text] [PDF] |
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Y. Birnbaum, Y. Ye, S. Rosanio, S. Tavackoli, Z.-Y. Hu, E. R. Schwarz, and B. F. Uretsky Prostaglandins mediate the cardioprotective effects of atorvastatin against ischemia-reperfusion injury Cardiovasc Res, February 1, 2005; 65(2): 345 - 355. [Abstract] [Full Text] [PDF] |
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A. Cordle and G. Landreth 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Inhibitors Attenuate {beta}-Amyloid-Induced Microglial Inflammatory Responses J. Neurosci., January 12, 2005; 25(2): 299 - 307. [Abstract] [Full Text] [PDF] |
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