on May 23, 2002
Arteriosclerosis, Thrombosis, and Vascular Biology. 2002
Published online before print May 23, 2002, doi: 10.1161/01.ATV.0000022694.16328.CC
Published online before print May 23, 2002, doi: 10.1161/01.ATV.0000022694.16328.CC
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on February 20, 2002
Accepted on April 8, 2002
Simvastatin Reduces Expression of Cytokines Interleukin-6, Interleukin-8, and Monocyte Chemoattractant Protein-1 in Circulating Monocytes From Hypercholesterolemic Patients
Abdolreza Rezaie-Majd ;
From the Clinic of Internal Medicine II (A.R.-M., T.M., R.A.B., E.M., M.B.), Department of Angiology, the Department of Internal Medicine I (P.V.), Division of Hematology and Hemostaseology, the Department of Cardiothoracic Surgery (M.R.M.), the Department of Gynecology and Obstetrics (P.H.), and the Department of Anesthesiology and General Intensive Care (A.K.), Unit A, University of Vienna, Vienna, Austria.
* To whom correspondence should be addressed. E-mail: Mehrdad.Baghestanian{at}univie.ac.at.
Objective—A number of studies have shown that statins decrease morbidity and mortality in patients with cardiovascular diseases. The anti-inflammatory effects of statins have recently been implicated in the clinical benefit that can be obtained in the treatment of atherosclerosis. Little is known about the mechanisms by which statins counteract inflammation.
Methods and Results—In this study, we asked whether simvastatin can influence in vitro and in vivo production of the proinflammatory cytokines interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1. A total of 107 hypercholesterolemic patients were treated with simvastatin. As measured by ELISA, serum levels of cytokines significantly decreased after 6 weeks of treatment (P<0.05). Furthermore, simvastatin decreased the expression of IL-6, IL-8, and monocyte chemoattractant protein-1 mRNA in peripheral blood mononuclear cells. Similar results were obtained in vitro by using cultured human umbilical vein endothelial cells and peripheral blood mononuclear cells from healthy normolipemic donors. Exposure to simvastatin, atorvastatin, or cerivastatin caused downregulation of the expression of cytokine mRNA in a time- and dose-dependent manner. Furthermore, all statins tested were able to reduce the concentrations of cytokines in cellular and extracellular fractions of human umbilical vein endothelial cells (P<0.05).
Conclusions—Our data show that simvastatin is anti-inflammatory through the downregulation of cytokines in the endothelium and leukocytes. These effects may explain some of the clinical benefits of these drugs in the treatment of atherosclerosis.
Key words: atherosclerosis • inflammation • statins • chemokines • cytokines • serum levels • interleukins • monocyte chemoattractant protein
This article has been cited by other articles:
 |
|
 |
|
  J. A. Benton, H. B. Kern, L. A. Leinwand, P. D. Mariner, and K. S. Anseth Statins Block Calcific Nodule Formation of Valvular Interstitial Cells by Inhibiting {alpha}-Smooth Muscle Actin Expression Arterioscler Thromb Vasc Biol, November 1, 2009; 29(11): 1950 - 1957. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Obi, W. Wysokinski, K. Karnicki, W. G. Owen, and R. D. McBane II Inhibition of Platelet-Rich Arterial Thrombus In Vivo: Acute Antithrombotic Effect of Intravenous HMG-CoA Reductase Therapy Arterioscler Thromb Vasc Biol, September 1, 2009; 29(9): 1271 - 1276. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Apostolakis, K. Vogiatzi, V. Amanatidou, and D. A. Spandidos Interleukin 8 and cardiovascular disease Cardiovasc Res, August 4, 2009; (2009) cvp241v2. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Alvarez, C. Municio, S. Alonso, J. A. S. Roman, M. S. Crespo, and N. Fernandez Cyclooxygenase-2 Induced by Zymosan in Human Monocyte-Derived Dendritic Cells Shows High Stability, and Its Expression Is Enhanced by Atorvastatin J. Pharmacol. Exp. Ther., June 1, 2009; 329(3): 987 - 994. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. P. Phipps and N. Blumberg Statin Islands and PPAR Ligands in Platelets Arterioscler Thromb Vasc Biol, May 1, 2009; 29(5): 620 - 621. [Full Text] [PDF]
|
|
|
|
|
|
R. Virmani, A. V. Finn, and F. D. Kolodgie Carotid Plaque Stabilization and Progression After Stroke or TIA Arterioscler Thromb Vasc Biol, January 1, 2009; 29(1): 3 - 6. [Full Text] [PDF]
|
|
|
|
|
|
K. Shimizu and R. N. Mitchell The Role of Chemokines in Transplant Graft Arterial Disease Arterioscler Thromb Vasc Biol, November 1, 2008; 28(11): 1937 - 1949. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F. Kircher, J. Grimm, F. K. Swirski, P. Libby, R. E. Gerszten, J. R. Allport, and R. Weissleder Noninvasive In Vivo Imaging of Monocyte Trafficking to Atherosclerotic Lesions Circulation, January 22, 2008; 117(3): 388 - 395. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. S. Fedson and F. Frost Statin Protection Against Influenza and COPD Mortality Chest, October 1, 2007; 132(4): 1406 - 1407. [Full Text] [PDF]
|
|
|
|
 |
|
 R. Yin, J. Zhu, Z. Wang, H. Huang, J. Qian, Z. Li, and H. Jing Simvastatin attenuates cardiac isograft ischemia-reperfusion injury by down-regulating CC chemokine receptor-2 expression J. Thorac. Cardiovasc. Surg., September 1, 2007; 134(3): 780 - 788. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Jialal, E. Miguelino, S. C. Griffen, and S. Devaraj Concomitant Reduction of Low-Density Lipoprotein-Cholesterol and Biomarkers of Inflammation with Low-Dose Simvastatin Therapy in Patients with Type 1 Diabetes J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 3136 - 3140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. J. Frost, H. Petersen, K. Tollestrup, and B. Skipper Influenza and COPD Mortality Protection as Pleiotropic, Dose-Dependent Effects of Statins Chest, April 1, 2007; 131(4): 1006 - 1012. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Devaraj, E. Chan, and I. Jialal Direct Demonstration of an Antiinflammatory Effect of Simvastatin in Subjects with the Metabolic Syndrome J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4489 - 4496. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A.N. Verhoeven, F. L. Moll, J. A.F. Koekkoek, A. C. van der Wal, D. P.V. de Kleijn, J. P. P.M. de Vries, J. H. Verheijen, E. Velema, E. Busser, A. Schoneveld, et al. Statin Treatment Is Not Associated With Consistent Alterations in Inflammatory Status of Carotid Atherosclerotic Plaques: A Retrospective Study in 378 Patients Undergoing Carotid Endarterectomy Stroke, August 1, 2006; 37(8): 2054 - 2060. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Giri, M. M. McDermott, P. Greenland, J. M. Guralnik, M. H. Criqui, K. Liu, L. Ferrucci, D. Green, J. R. Schneider, and L. Tian Statin Use and Functional Decline in Patients With and Without Peripheral Arterial Disease J. Am. Coll. Cardiol., March 7, 2006; 47(5): 998 - 1004. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Marketou, E. A. Zacharis, D. Nikitovic, E. S. Ganotakis, F. I. Parthenakis, N. Maliaraki, and P. E. Vardas Early Effects of Simvastatin versus Atorvastatin on Oxidative Stress and Proinflammatory Cytokines in Hyperlipidemic Subjects Angiology, March 1, 2006; 57(2): 211 - 218. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Yilmaz, C. Reiss, A. Weng, I. Cicha, C. Stumpf, A. Steinkasserer, W. G. Daniel, and C. D. Garlichs Differential effects of statins on relevant functions of human monocyte-derived dendritic cells J. Leukoc. Biol., March 1, 2006; 79(3): 529 - 538. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. B. Holven, J. K. Damas, A. Yndestad, T. Waehre, T. Ueland, B. Halvorsen, L. Heggelund, W. J. Sandberg, A. G. Semb, S. S. Froland, et al. Chemokines in Children With Heterozygous Familiar Hypercholesterolemia: Selective Upregulation of RANTES Arterioscler Thromb Vasc Biol, January 1, 2006; 26(1): 200 - 205. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Pirat, P. Zeyneloglu, D. Aldemir, M. Yucel, O. Ozen, S. Candan, and G. Arslan Pretreatment with Simvastatin Reduces Lung Injury Related to Intestinal Ischemia-Reperfusion in Rats Anesth. Analg., January 1, 2006; 102(1): 225 - 232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. K. Ray and C. P. Cannon The Potential Relevance of the Multiple Lipid-Independent (Pleiotropic) Effects of Statins in the Management of Acute Coronary Syndromes J. Am. Coll. Cardiol., October 18, 2005; 46(8): 1425 - 1433. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Yamagami, K. Kitagawa, T. Hoshi, S. Furukado, H. Hougaku, Y. Nagai, and M. Hori Associations of Serum IL-18 Levels With Carotid Intima-Media Thickness Arterioscler Thromb Vasc Biol, July 1, 2005; 25(7): 1458 - 1462. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. H. Han, J. Ryu, K. H. Hong, J. Ko, Y. K. Pak, J.-B. Kim, S. W. Park, and J. J. Kim HMG-CoA Reductase Inhibition Reduces Monocyte CC Chemokine Receptor 2 Expression and Monocyte Chemoattractant Protein-1-Mediated Monocyte Recruitment In Vivo Circulation, March 22, 2005; 111(11): 1439 - 1447. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. O'Neil-Callahan, G. Katsimaglis, M. R. Tepper, J. Ryan, C. Mosby, J. P.A. Ioannidis, and P. G. Danias Statins decrease perioperative cardiac complications in patients undergoing noncardiac vascular surgery: The Statins for Risk Reduction in Surgery (StaRRS) study J. Am. Coll. Cardiol., February 1, 2005; 45(3): 336 - 342. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Tedgui The role of inflammation in atherothrombosis: implications for clinical practice Vascular Medicine, February 1, 2005; 10(1): 45 - 53. [Abstract] [PDF]
|
|
|
|
|
|
J. Pleiner, G. Schaller, F. Mittermayer, S. Zorn, C. Marsik, S. Polterauer, S. Kapiotis, and M. Wolzt Simvastatin Prevents Vascular Hyporeactivity During Inflammation Circulation, November 23, 2004; 110(21): 3349 - 3354. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Deo, A. Khera, D. K. McGuire, S. A. Murphy, J. de P. Meo Neto, D. A. Morrow, and J. A. de Lemos Association among plasma levels of monocyte chemoattractant protein-1, traditional cardiovascular risk factors, and subclinical atherosclerosis J. Am. Coll. Cardiol., November 2, 2004; 44(9): 1812 - 1818. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. McGowan and for the Treating to New Target Study Group There Is No Evidence for an Increase in Acute Coronary Syndromes After Short-Term Abrupt Discontinuation of Statins in Stable Cardiac Patients Circulation, October 19, 2004; 110(16): 2333 - 2335. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Schillinger, M. Exner, W. Mlekusch, J. Amighi, S. Sabeti, M. Muellner, H. Rumpold, O. Wagner, and E. Minar Statin therapy improves cardiovascular outcome of patients with peripheral artery disease Eur. Heart J., May 1, 2004; 25(9): 742 - 748. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Nomura, A. Shouzu, S. Omoto, M. Nishikawa, and T. Iwasaka Effects of Losartan and Simvastatin on Monocyte-Derived Microparticles in Hypertensive Patients With and Without Type 2 Diabetes Mellitus Clinical and Applied Thrombosis/Hemostasis, April 1, 2004; 10(2): 133 - 141. [Abstract] [PDF]
|
|
|
|
|
|
H. Yamagami, K. Kitagawa, Y. Nagai, H. Hougaku, M. Sakaguchi, K. Kuwabara, K. Kondo, T. Masuyama, M. Matsumoto, and M. Hori Higher Levels of Interleukin-6 Are Associated With Lower Echogenicity of Carotid Artery Plaques Stroke, March 1, 2004; 35(3): 677 - 681. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Dziedzic, A. Slowik, A. Szczudlik, M. Schwaninger, A. Grau, and D. Acalovschi Interleukin-6 and Stroke: Cerebral Ischemia Versus Nonspecific Factors Influencing Interleukin-6 * Response Stroke, December 1, 2003; 34 (12): e229 - e230. [Full Text] [PDF]
|
|
|
|
|
|
K. Shimizu, M. Aikawa, K. Takayama, P. Libby, and R. N. Mitchell Direct Anti-Inflammatory Mechanisms Contribute to Attenuation of Experimental Allograft Arteriosclerosis by Statins Circulation, October 28, 2003; 108(17): 2113 - 2120. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Kleemann, H. M.G. Princen, J. J. Emeis, J. W. Jukema, R. D. Fontijn, A. J.G. Horrevoets, T. Kooistra, and L. M. Havekes 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, September 16, 2003; 108(11): 1368 - 1374. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Pierre-Paul and V. Gahtan Noncholesterol-Lowering Effects of Statins Vascular and Endovascular Surgery, September 1, 2003; 37(5): 301 - 313. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Schachter Review: Lipid lowering drugs, inflammation and cardiovascular disease The British Journal of Diabetes & Vascular Disease, May 1, 2003; 3(3): 178 - 182. [Abstract] [PDF]
|
|
|
|
|
|
S. Wolfrum, K. S. Jensen, and J. K. Liao Endothelium-Dependent Effects of Statins Arterioscler Thromb Vasc Biol, May 1, 2003; 23(5): 729 - 736. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-P. Despres, I. Lemieux, A. Pascot, N. Almeras, M. Dumont, A. Nadeau, J. Bergeron, and D. Prud'homme Gemfibrozil Reduces Plasma C-Reactive Protein Levels in Abdominally Obese Men With the Atherogenic Dyslipidemia of the Metabolic Syndrome Arterioscler Thromb Vasc Biol, April 1, 2003; 23(4): 702 - 703. [Full Text] [PDF]
|
|
|
|
|
|
A. Rezaie-Majd, G. W. Prager, R. A. Bucek, G. H. Schernthaner, T. Maca, H.-G. Kress, P. Valent, B. R. Binder, E. Minar, and M. Baghestanian Simvastatin Reduces the Expression of Adhesion Molecules in Circulating Monocytes From Hypercholesterolemic Patients Arterioscler Thromb Vasc Biol, March 1, 2003; 23(3): 397 - 403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. McDermott, J. M. Guralnik, P. Greenland, W. H. Pearce, M. H. Criqui, K. Liu, L. Taylor, C. Chan, L. Sharma, J. R. Schneider, et al. Statin Use and Leg Functioning in Patients With and Without Lower-Extremity Peripheral Arterial Disease Circulation, February 11, 2003; 107(5): 757 - 761. [Abstract] [Full Text] [PDF]
|
|