A Clinical Evaluation of Statin Pleiotropy: Statins Selectively and Dose-Dependently Reduce Vascular Inflammation

PLoS ONE

Volumn 8, Issue 1, 2013, Pages

  van der Meij, Evelien ^a   Koning, Giel G ^b   Vriens, Patrick W ^b   Peeters, Marcel F ^b   Meijer, C Arnoud ^a   Kortekaas, Kim E ^a,d   Dalman, Ronald L ^d   van Bockel, J Hajo ^a   Hanemaaijer, Roeland ^c   Kooistra, Teake ^c   Kleemann, Robert ^c   Lindeman, Jan H N ^a  

^a LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

^b Microvida Laboratory for Medical Microbiology and Immunology   (Netherlands)

^c TNO   (Netherlands)

^d STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ATORVASTATIN; CATHEPSIN K; CATHEPSIN S; DOXYCYCLINE; GAMMA INTERFERON; GRANULOCYTE COLONY STIMULATING FACTOR; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 1; INTERLEUKIN 6; MACROPHAGE INFLAMMATORY PROTEIN 1ALPHA; MACROPHAGE INFLAMMATORY PROTEIN 1BETA; MONOCYTE CHEMOTACTIC PROTEIN 1; PLACEBO; SIMVASTATIN; TUMOR NECROSIS FACTOR ALPHA;

ABDOMINAL AORTA ANEURYSM; ADULT; AGED; ANTIINFLAMMATORY ACTIVITY; ARTICLE; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DISEASE COURSE; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG MEGADOSE; DRUG POTENCY; DRUG SAFETY; ENZYME ACTIVITY; FEMALE; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; MACROPHAGE; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; OBSERVATIONAL STUDY; PHENOTYPE; PLEIOTROPY; POLARIZATION; PROSPECTIVE STUDY; PROTEIN ANALYSIS; TREATMENT DURATION; TREATMENT RESPONSE;

AGED; AGED, 80 AND OVER; ANTI-INFLAMMATORY AGENTS; AORTA; AORTIC ANEURYSM, ABDOMINAL; B-LYMPHOCYTES; BIOLOGICAL MARKERS; CELL DIFFERENTIATION; CHEMOKINES; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; LEUKOCYTES; MACROPHAGES; MALE; MIDDLE AGED; NF-KAPPA B; T-LYMPHOCYTES;

EID: 84872795405     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0053882     Document Type: Article

References (43)

1. Jain MK, Ridker PM, (2005) Anti-inflammatory effects of statins: clinical evidence and basic mechanisms. Nat Rev Drug Discov 4: 977-987.
2. Zhou Q, Liao JK, (2010) Pleiotropic effects of statins.- Basic research and clinical perspectives-. Circ J 74: 818-26.
3. Verschuren L, Kleemann R, Offerman EH, Szalai AJ, Emeis SJ, et al. (2005) Effect of low dose atorvastatin versus diet-induced cholesterol lowering on atherosclerotic lesion progression and inflammation in apolipoprotein E*3-Leiden transgenic mice. Arterioscler Thromb Vasc Biol 25: 161-167.
4. Kleemann R, Princen HM, Emeis JJ, Jukema JW, Fontijn RD, et al. (2003) Rosuvastatin reduces atherosclerosis development beyond and independent of its plasma cholesterol-lowering effect in APOE*3-Leiden transgenic mice: evidence for antiinflammatory effects of rosuvastatin. Circulation 108: 1368-74.
5. Shaw SM, Fildes JE, Yonan N, Williams SG, (2009) Pleiotropic effects and cholesterol-lowering therapy. Cardiology 112: 4-12.
6. Rizas KD, Ippagunta N, Tilson MD 3rd, (2009) Immune cells and molecular mediators in the pathogenesis of the abdominal aortic aneurysm. Cardiol Rev 17: 201-10.
7. Lindeman JH, Abdul-Hussien H, Schaapherder AF, Van Bockel JH, Von der Thüsen JH, et al. (2008) Enhanced expression and activation of pro-inflammatory transcription factors distinguish aneurysmal from atherosclerotic aorta: IL-6- and IL-8-dominated inflammatory responses prevail in the human aneurysm. Clin Sci(Lond) 114: 687-97.
8. Diehm N, Baumgartner I, (2009) Determinants of aneurysmal aortic disease. Circulation 119: 2134-2135.
9. Friedewald WT, Levy RI, Fredrickson DS, (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18: 499-502.
10. Haslinger B, Kleemann R, Toet KH, Kooistra T, (2003) Simvastatin suppresses tissue factor expression and increases fibrinolytic activity in tumor necrosis factor-alpha-activated human peritoneal mesothelial cells. Kidney Int 63: 2065-74.
11. Abdul-Hussien H, Soekhoe RG, Weber E, von der Thüsen JH, Kleemann R, et al. (2007) Collagen degradation in the abdominal aneurysm: a conspiracy of matrix metalloproteinase and cysteine collagenases. Am J Pathol 170: 809-17.
12. Kleemann R, van Erk M, Verschuren L, van den Hoek AM, Koek M, et al. (2010) Time-resolved and tissue-specific systems analysis of the pathogenesis of insulin resistance. PLoS One 5: e8817.
13. Kleemann R, Gervois PP, Verschuren L, Staels B, Princen HM, et al. (2003) Fibrates down-regulate IL-1-stimulated C-reactive protein gene expression in hepatocytes by reducing nuclear p50-NFkappa B-C/EBP-beta complex formation. Blood 101: 545-551.
14. Lindeman JH, Abdul-Hussien H, van Bockel JH, Wolterbeek R, Kleemann R, (2009) Clinical trial of doxycycline for matrix metalloproteinase-9 inhibition in patients with an abdominal aneurysm: doxycycline selectively depletes aortic wall neutrophils and cytotoxic T cells. Circulation 119: 2209-16.
15. Fitzmaurice GM, Ravichandran C, (2008) A primer in longitudinal data analysis. Circulation 118: 2005-10.
16. Zhou Z, Rahme E, Pilote L, (2006) Are statins created equal? Evidence from randomized trials of pravastatin, simvastatin, and atorvastatin for cardiovascular disease prevention. Am Heart J 151: 273-81.
17. Robinson JG, (2008) Models for describing relations among the various statin drugs, low-density lipoprotein cholesterol lowering, pleiotropic effects, and cardiovascular risk. Am J Cardiol 101: 1009-15.
18. Goldstein LB, Adams R, Alberts MJ, Appel LJ, Brass LM, et al. (2006) Primary prevention of ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council: cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation 113: e873-923.
19. Kinlay S, Schwartz GG, Olsson AG, Rifai N, Szarek M, et al. (2008) Inflammation, statin therapy, and risk of stroke after an acute coronary syndrome in the MIRACL study. Arterioscler Thromb Vasc Biol 28: 142-7.
20. Kleemann R, Verschuren L, de Rooij BJ, Lindeman J, de Maat MM, et al. (2004) Evidence for anti-inflammatory activity of statins and PPARalpha activators in human C-reactive protein transgenic mice in vivo and in cultured human hepatocytes in vitro. Blood 103: 4188-94.
21. Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, et al. (2006) ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. Circulation 113: e463-654.
22. Dawson J, Cockerill GW, Choke E, Belli AM, Loftus I, et al. (2007) Aortic aneurysms secrete interleukin-6 into the circulation. J Vasc Surg 45: 350-6.
23. Emerging Risk Factors Collaboration (2010) Kaptoge S, Di Angelantonio E, Lowe G, Pepys MB, et al. (2010) C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet 375: 132-40.
24. Kleemann R, Zadelaar S, Kooistra T, (2008) Cytokines and atherosclerosis: a comprehensive review of studies in mice. Cardiovasc Res 79: 360-76.
25. Ban K, Ikeda U, Takahashi M, Kanbe T, Kasahara T, et al. (1994) Expression of intercellular adhesion molecule-1 on rat cardiac myocytes by monocyte chemoattractant protein-1. Cardiovasc Res 1994; 28: 1258-62.
26. Charo IF, Taubman MB, (2004) Chemokines in the pathogenesis of vascular disease. Circ Res 95: 858-66.
27. Mantovani A, Sica A, Locati M, (2005) Macrophage polarization comes of age. Immunity 23: 344-6.
28. Pello OM, Silvestre C, De Pizzol M, Andrés V, (2011) A glimpse on the phenomenon of macrophage polarization during atherosclerosis. Immunobiology 216: 1172-6.
29. Wynn TA, Barron L, Thompson RW, Madala SK, Wilson MS, et al. (2011) Quantitative assessment of macrophage functions in repair and fibrosis. Curr Protoc Immunol. Chapter 14: Unit14.22.
30. Bühling F, Reisenauer A, Gerber A, Krüger S, Weber E, et al. (2001) Cathepsin K-a marker of macrophage differentiation? J Pathol 195: 375-82.
31. Zhao L, Moos MP, Gräbner R, Pédrono F, Fan J, et al. (2004) The 5-lipoxygenase pathway promotes pathogenesis of hyperlipidemia-dependent aortic aneurysm. Nat Med 10: 966-73.
32. Jaffer FA, Kim DE, Quinti L, Tung CH, Aikawa E, et al. (2007) Optical visualization of cathepsin K activity in atherosclerosis with a novel, protease-activatable fluorescence sensor. Circulation 115: 2292-8.
33. Abdul Rahman M, Khan JA, Mazari FA, Mockford K, McCollum PT, et al. (2011) A Randomized Placebo Controlled Trial of the Effect of Preoperative Statin Use on Matrix Metalloproteinases and Tissue Inhibitors of Matrix Metalloproteinases in Areas of Low and Peak Wall Stress in Patients Undergoing Elective Open Repair of Abdominal Aortic Aneurysm. Ann Vasc Surg 25: 32-8.
34. Lutgens SP, Cleutjens KB, Daemen MJ, Heeneman S, (2007) Cathepsin cysteine proteases in cardiovascular disease. FASEB J 21: 3029-41.
35. Sun J, Sukhova GK, Zhang J, Chen H, Sjöberg S, et al. (2012) Cathepsin K deficiency reduces elastase perfusion-induced abdominal aortic aneurysms in mice. Arterioscler Thromb Vasc Biol 32: 15-23.
36. Thompson RW, Curci JA, Ennis TL, Mao D, Pagano MB, et al. (2006) Pathophysiology of abdominal aortic aneurysms: insights from the elastase-induced model in mice with different genetic backgrounds. Ann N Y Acad Sci 1085: 59-73.
37. Sukhova GK, Shi GP, (2006) Do cathepsins play a role in abdominal aortic aneurysm pathogenesis? Ann N Y Acad Sci 1085: 161-9.
38. Rådmark O, Samuelsson B, (2007) 5-lipoxygenase: regulation and possible involvement in atherosclerosis. Prostaglandins Other Lipid Mediat 83: 162-74.
39. Amsen D, Spilianakis CG, Flavell RA, (2009) How are T(H)1 and T(H)2 effector cells made? Curr Opin Immunol 21: 153-60.
40. Lu H, Rateri DL, Cassis LA, Daugherty A, (2008) The role of the renin-angiotensin system in aortic aneurysmal diseases. Curr Hypertens Rep 10: 99-106.
41. Takagi H, Matsui M, Umemoto T, (2010) A meta-analysis of clinical studies of statins for prevention of abdominal aortic aneurysm expansion. J Vasc Surg 52: 1675-81.
42. Ferguson CD, Clancy P, Bourke B, Walker PJ, Dear A, et al. (2010) Association of statin prescription with small abdominal aortic aneurysm progression. Am Heart J 159: 307-13.
43. Dunne JA, Bailey MA, Griffin KJ, Sohrabi S, Coughlin PA, et al. (2012) Statins: The Holy Grail of Abdominal Aortic Aneurysm (AAA) Growth Attenuation? A Systematic Review of the Literature. Curr Vasc Pharmacol. Epub ahead of print.