Home Atorvastatin suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells
Article
Licensed
Unlicensed Requires Authentication

Atorvastatin suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells

  • Katharina Schroecksnadel , Barbara Frick , Christiana Winkler , Barbara Wirleitner , Günter Weiss and Dietmar Fuchs
Published/Copyright: September 21, 2011

Abstract

Hyperhomocysteinemia is regarded as an independent risk factor for vascular diseases, and homocysteine is supposed to contribute to oxidative stress and endothelial damage. Statin therapy is an established intervention to reduce the risk of acute events in patients suffering from cardiovascular diseases. Apart from their lipid-lowering capacity, statins also exert anti-inflammatory and antioxidant effects. As cellular immune activation and oxidative stress play a major role in the pathogenesis of cardiovascular diseases, the anti-inflammatory capacity of statins could partly be responsible for the beneficial effects observed in patients. Earlier we reported that stimulated peripheral blood mononuclear cells (PBMCs) release homocysteine. Here we studied the influence of atorvastatin on homocysteine production in stimulated PBMCs and compared changes in cysteine concentrations and in neopterin production, which is a sensitive indicator of cellular immune activation. Stimulation of human PBMCs with the mitogens concanavalin A and phytohemagglutinin induced significant homocysteine and neopterin production compared to unstimulated cells, whereas cysteine concentrations remained unchanged. Treatment of PBMCs with increasing doses of atorvastatin (10–100μM) suppressed both biochemical pathways in a dose-dependent manner, and cell proliferation was inhibited in parallel. Again, cysteine levels were not influenced by any treatment. The down-regulating effect of atorvastatin on homocysteine formation in vitro indicates that statins may prevent homocysteine accumulation in the blood via immunosuppression.


Corresponding author: Dietmar Fuchs, Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Fritz Pregl Str. 3, 6020 Innsbruck, Austria Phone: +43-512-507-3519, Fax: +43-512-507-2865,

References

1. Auer J, Eber B. A clinical focus on statins. Curr Opin Invest Drugs 2001; 2:382–8.Search in Google Scholar

2. Kwak B, Mulhaupt F, Myit S, Mach F. Statins as a newly recognized type of immunomodulator. Nat Med 2000; 6:1399–402.10.1038/82219Search in Google Scholar

3. Franzoni F, Quinones-Galvan A, Regoli F, Ferrannini E, Galetta F. A comparative study of the in vitro antioxidant activity of statins. Int J Cardiol 2003; 90:317–21.10.1016/S0167-5273(02)00577-6Search in Google Scholar

4. Tsiara S, Elisaf M, Mikhailidis DP. Early vascular benefits of statin therapy. Curr Med Res Opin 2003; 19:540–56.10.1185/030079903125002225Search in Google Scholar

5. Yoshida M. Potential role of statins in inflammation and atherosclerosis. J Atheroscler Thromb 2003; 10:140–4.10.5551/jat.10.140Search in Google Scholar

6. Neurauter G, Wirleitner B, Laich A, Schennach H, Weiss G, Fuchs D. Atorvastatin suppresses interferon-gamma-induced neopterin formation and tryptophan degradation in human peripheral blood mononuclear cells and in monocytic cell lines. Clin Exp Immunol 2003; 131:264–7.10.1046/j.1365-2249.2003.02021.xSearch in Google Scholar

7. Weiss G, Willeit J, Kiechl S, Fuchs D, Jarosch E, Oberhollenzer F, et al. Increased concentrations of neopterin in carotid atherosclerosis. Atherosclerosis 1994; 106:263–71.10.1016/0021-9150(94)90131-7Search in Google Scholar

8. Zouridakis E, Avanzas P, Arroyo-Espliguero R, Fredericks S, Kaski JC. Markers of inflammation and rapid coronary artery disease progression in patients with stable angina pectoris. Circulation 2004 28; 110:1747–53.10.1161/01.CIR.0000142664.18739.92Search in Google Scholar PubMed

9. Frick B, Rudzite V, Schröcksnadel K, Kalnins U, Erglis A, Trusinskis K, et al. Homocysteine, B vitamins and immune activation in coronary heart disease. Pteridines 2003; 14:82–7.10.1515/pteridines.2003.14.3.82Search in Google Scholar

10. Schroecksnadel K, Frick B, Wirleitner B, Winkler C, Schennach H, Fuchs D. Moderate hyperhomocysteinemia and immune activation. Curr Pharm Biotechnol 2004; 5:107–18.10.2174/1389201043489657Search in Google Scholar PubMed

11. Schroecksnadel K, Frick B, Wirleitner B, Schennach H, Fuchs D. Homocysteine accumulates in supernatants of stimulated human peripheral blood mononuclear cells. Clin Exp Immunol 2003; 134:53–6.10.1046/j.1365-2249.2003.02251.xSearch in Google Scholar PubMed PubMed Central

12. James SP. Measurement of basic immunologic characteristics of human mononuclear cells. In: Coligan JE, Margulies DH, Shevach EM, Strober W, Kruisbeek A, editors. Current protocols in immunology. New York: John Wiley & Sons, 1991: Chapter 7, unit 7.1.Search in Google Scholar

13. Frick B, Schroecksnadel K, Neurauter G, Wirleitner B, Artner-Dworzak E, Fuchs D. Rapid measurement of total plasma homocysteine by HPLC. Clin Chim Acta 2003; 331:19–23.10.1016/S0009-8981(03)00076-7Search in Google Scholar

14. Schroecksnadel K, Frick B, Winkler C, Wirleitner B, Schennach H, Fuchs D. Aspirin down-regulates homocysteine formation in stimulated human peripheral blood mononuclear cells. Scand J Immunol 2005; 62:155–60.10.1111/j.1365-3083.2005.01654.xSearch in Google Scholar

15. Winkler C, Wirleitner B, Schroecksnadel K, Schennach H, Mur E, Fuchs D. St. John's wort (Hypericum perforatum) counteracts cytokine-induced tryptophan catabolism in vitro. Biol Chem 2004; 385:1197–202.10.1515/BC.2004.155Search in Google Scholar

16. van den Brandhof WE, Haks K, Schouten EG, Verhoef P. The relation between plasma cysteine, plasma homocysteine and coronary atherosclerosis. Atherosclerosis 2001; 157:403–9.10.1016/S0021-9150(00)00724-3Search in Google Scholar

17. Libby P. Inflammation in atherosclerosis. Nature 2002; 420:868–74.10.1038/nature01323Search in Google Scholar

18. Young JL, Libby P, Schonbeck U. Cytokines in the pathogenesis of atherosclerosis. Thromb Haemost 2002; 88:554–67.10.1055/s-0037-1613256Search in Google Scholar

19. Heitzer T, Schlinzig T, Krohn K, Meinertz T, Munzel T. Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease. Circulation 2001; 104:2673–8.10.1161/hc4601.099485Search in Google Scholar

20. Dudman NP, Hicks C, Wang J, Wilcken DE. Human arterial endothelial cell detachment in vitro: its promotion by homocysteine and cysteine. Atherosclerosis 1991; 91:77–83.10.1016/0021-9150(91)90189-ASearch in Google Scholar

21. Wall RT, Harlan JM, Harker LA, Striker GE. Homocysteine-induced endothelial cell injury in vitro: a model for the study of vascular injury. Thromb Res 1980; 18:113–21.10.1016/0049-3848(80)90175-9Search in Google Scholar

22. Milionis HJ, Papakostas J, Kakafika A, Chasiotis G, Seferiadis K, Elisaf MS. Comparative effects of atorvastatin, simvastatin, and fenofibrate on serum homocysteine levels in patients with primary hyperlipidemia. J Clin Pharmacol 2003; 43:825–30.10.1177/0091270003255920Search in Google Scholar PubMed

23. Giral P, Bruckert E, Jacob N, Chapman MJ, Foglietti MJ, Turpin G. Homocysteine and lipid lowering agents. A comparison between atorvastatin and fenofibrate in patients with mixed hyperlipidemia. Atherosclerosis 2001; 154:421–7.10.1016/S0021-9150(00)00474-3Search in Google Scholar

24. Walter RB, Fuchs D, Weiss G, Walter TR, Reinhart WH. HMG-CoA reductase inhibitors are associated with decreased serum neopterin levels in stable coronary artery disease. Clin Chem Lab Med 2003; 41:1314–9.10.1515/CCLM.2003.200Search in Google Scholar PubMed

Received: 2005-8-16
Accepted: 2005-9-13
Published Online: 2011-9-21
Published in Print: 2005-12-1

©2005 by Walter de Gruyter Berlin New York

Articles in the same Issue

  1. Contents Volume 43, 2005
  2. Author Index
  3. Subject Index
  4. ProteinChips: the essential tools for proteomic biomarker discovery and future clinical diagnostics
  5. Protein profiling as a diagnostic tool in clinical chemistry: a review
  6. Protein biochip systems for the clinical laboratory
  7. Automation of biochip array technology for quality results
  8. SELDI-TOF-MS proteomics of breast cancer
  9. Protein microarrays for the diagnosis of allergic diseases: state-of-the-art and future development
  10. Separation of human serum proteins using the Beckman-Coulter PF2D™ system: analysis of ion exchange-based first dimension chromatography
  11. Rapid, accurate genotyping of alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 based on the use of denaturing HPLC
  12. APOA1 polymorphisms are associated with variations in serum triglyceride concentrations in hypercholesterolemic individuals
  13. Simple PCR heteroduplex, SSCP mutation screening methods for the detection of novel catalase mutations in Hungarian patients with type 2 diabetes mellitus
  14. Glycogen phosphorylase BB in acute coronary syndromes
  15. Alteration in serum leptin correlates with alterations in serum N-telopeptide of collagen type I and serum osteocalcin during the progression of osteoporosis in ovariectomized rats
  16. Glycemic control in diabetes in three Danish counties
  17. Atorvastatin suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells
  18. Buprenorphine detection in biological samples
  19. The effect of thyroid antibody positivity on reference intervals for thyroid stimulating hormone (TSH) and free thyroxine (FT4) in an aged population
  20. High-affinity antibodies in a new immunoassay for plasma tissue factor: reduction in apparent intra-individual variation
  21. Physiological matrix metalloproteinase concentrations in serum during childhood and adolescence, using Luminex® Multiplex technology
  22. Sensitive immunoassays for the autoantibodies reacting against citrullinated carboxy-terminal telopeptides of type I and type II collagens in patients with rheumatoid arthritis
  23. Acknowledgement
Downloaded on 11.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/CCLM.2005.234/html
Scroll to top button