1. bookVolume 22 (2014): Issue 4 (December 2014)
Journal Details
License
Format
Journal
eISSN
2284-5623
First Published
08 Aug 2013
Publication timeframe
4 times per year
Languages
English
access type Open Access

Flow Cytometry Analysis of Pparα Receptors in Metabolic Syndrome / Studiul Receptorilor Pparα prin Metoda Citometriei în Flux în Sindromul Metabolic

Published Online: 30 Dec 2014
Page range: 427 - 438
Received: 15 Jun 2014
Accepted: 03 Oct 2014
Journal Details
License
Format
Journal
eISSN
2284-5623
First Published
08 Aug 2013
Publication timeframe
4 times per year
Languages
English
Abstract

Introduction. Metabolic syndrome (MS) is a cluster of distinct metabolic alterations with an increased cardiovascular risk. Peroxisome Proliferator-Activated Receptor - Alpha (PPARα), member of the nuclear receptor superfamily of transcription factors, is critically involved in the management of lipid metabolism during homeostasis or inflammatory stresses in various cell types and represents one of the therapeutic targets in MS. We analysed the PPARα expression in leukocytes of pacients with MS, in order to address PPARα involvement in these group of diseases. Material and method. Our study included 57 adult patients recruited under informed voluntary consent, investigated in order to establish whether they present MS, according to International Diabetes Federation (IDF) European guidelines and grouped in 2 lots: the MS Lot (26 patients) and control group, non-MS Lot (31 subjects). Common clinical and laboratory parameters targeted in MS evaluation were determined for all the studied cases. The expression levels of 2 molecules, PPARα and CD36 were evaluated in various circulating leukocyte populations of these patients by an optimized flow cytometry method. Statistic analysis clarifying the significance of value differences for various parameters measured was performed under SPSS and simple statistical tests (Pearson, t-Student, Chi -test). Results and discussion. The fluorescence staining for PPARα were significantly dimmer when comparing the cellular expression in eosinophils (p<0.05) of MS versus the Control group of subjects. Conclusions: Our study is the first to show that circulating eosinophils display significantly reduced PPARα protein expression in MS patients. The differences in key molecule expression in circulating leukocytes (like PPAR species, CD36, and other) might be evocatory for the endothelial dysfunction and obesity and might be of use in the therapeutic decision.

Keywords

Cuvinte cheie

1. Eckel R, Alberti KGMM, Grundy SM, Zimmet PZ. The metabolic syndrome. The Lancet. 2010;375(9710):181-3. DOI: 10.1016/S0140-6736(09)61794-310.1016/S0140-6736(09)61794-3Search in Google Scholar

2. Kahn R. Metabolic syndrome- what is the clinical usefulness? The Lancet. 2008;371(9628):1892-3. DOI: 10.1016/S0140-6736(08)60731-X10.1016/S0140-6736(08)60731-XSearch in Google Scholar

3. Reaven GM. The metabolic syndrome: is this diagnosis necessary? Am J Clin Nutr. 2006; 83(6):1237-7.10.1093/ajcn/83.6.123716762930Search in Google Scholar

4. Gami AS, Witt BJ, Howard DE, Erwin PJ, Gami LA, Somers VK et al. Metabolic Syndrome and Risk of Incident Cardiovascular Events and Death : a systematic review and meta-analysis of longitudinal studies, J Am Coll Cardiol. 2007;49(5):403-4. DOI: 10.1016/j. jacc.2006.09.032Search in Google Scholar

5. International Diabetes Federation. IDF Diabetes Atlas, 6th edn. International Diabetes Federation, Belgium, Brussels, 2013:1-155.Search in Google Scholar

6. World Health Organization. Global Status Report on Noncommunicable Diseases 2010. World Health Organization Geneva, Switzerland, 2011:1-176.Search in Google Scholar

7. Azhar S. Peroxisome proliferator-activated receptors, metabolic syndrome and cardiovascular disease. Future Cardiology.2010;6(5):657-91. DOI: 10.2217/fca.10.8610.2217/fca.10.86324674420932114Search in Google Scholar

8. Cercosimo E, Defronzo RA. Insulin resistance and endothelial dysfunction: the road map to cardiovascular diseases. Diabetes Metab Res Rev. 2006;22(6):423-36. DOI: 10.1002/dmrr.63410.1002/dmrr.63416506274Search in Google Scholar

9. Fruchart JCh. Peroxisome Proliferator-Activated Receptors at the Crossroads of Obesity, Diabetes and Cardiovascular Disease. Journal of American College Cardiology. 2006;48(9):24-32. DOI: 10.1016/j. jacc.2006.04.097Search in Google Scholar

10. Kersten S, Desvergne B, Wahli W. Roles of PPARS in health and disease. Nature. 2000;405(6785):421-4. DOI: 10.1038/3501300010.1038/3501300010839530Search in Google Scholar

11. Ricote M, Valledor AF, Glass CK. Decoding transcriptional programs regulated by PPARs and LXRs in the macrophage: effects on lipid homeostasis, inflammation, and atherosclerosis. Arteriosclerosis, Thrombosis and Vascular Biology. 2004;24(2):230-9. DOI: 10.1161/01.ATV.0000103951.67680.B110.1161/01.ATV.0000103951.67680.B114592855Search in Google Scholar

12. Straus DS, Glass CK. Anti-inflammatory actions of PPAR ligands: new insights on cellular and molecular mechanisms. Trends Immunol. 2007;28(12):551-8. DOI: 10.1016/j.it.2007.09.00310.1016/j.it.2007.09.00317981503Search in Google Scholar

13. Kersten S. Regulation of nutrient metabolism and inflammation. Meyerhof W, Beisiegel U, Joost H-G(Eds), Sensory and Metabolic Control of Energy Balance, Results and Problems in Cell Differentiation 52, Springer- Verlag Berlin Heidelberg, 2010: DOI:10.1007/978-3-642-14426-4_2. DOI: 10.1007/978-3-642-14426-4_210.1007/978-3-642-14426-4_220865368Search in Google Scholar

14. Silverstein R. Inflammation, atherosclerosis, and arterial thrombosis: Role of the scavenger receptor CD36. Cleveland Clinic Journal of Medicine. 2009;76(Suppl 2):S27-S30. DOI: 10.3949/ccjm.76.s2.0610.3949/ccjm.76.s2.06281053019376978Search in Google Scholar

15. Collot -Teixeira S, Martin J, McDermott-Roe C, Poston R, McGregor JL. CD36 and macrophages in atherosclerosis. Cardiovasc Resp. 2007;75(3):468-77. DOI: 10.1016/j.cardiores.2007.03.01010.1016/j.cardiores.2007.03.01017442283Search in Google Scholar

16. Herzenberg LA, Parks D, Sahaf B, Roederer M, Herzenberg LA. The history and future of the fluorescence activated cell sorter and flow cytometry: a view from Stanford. Clin Chem. 2002;48(10):1819-27.10.1093/clinchem/48.10.1819Search in Google Scholar

17. Sheikholeslami MR, Jilani I, Keating M, Uyeji J, Chen K, Kantarjian H et al. Variations in the detection of ZAP-70 in chronic lymphocytic leukemia: Comparison with IgV (H) mutation analysis. Cytometry B Clin Cytom. 2006;70(4):270-5. DOI: 10.1002/cyto.b.2013410.1002/cyto.b.2013416906585Search in Google Scholar

18. Butts CL, Shukair SA, Duncan KM, Harris CW, Belyavskaia E, Sternberg EM . Evaluation of steroid hormone receptor protein expression in intact cells using flow cytometry. Nucl Recept Signal. 2007; DOI:10.1621/nrs.05007. DOI: 10.1621/nrs.0500710.1621/nrs.05007194807217710123Search in Google Scholar

19. Christensen R. Testing Fisher, Neyman, Pearson and Bayes. American Statistician. 2005; 59(2):121-6. DOI: 10.1198/000313005X2087110.1198/000313005X20871Search in Google Scholar

20. Kreiner S, Christensen KB. Analysis of Local Dependence and Multi-dimensionality in Graphical Loglinear Rasch Models. Communications in Statistics - Theory and Methods. 2004;33(6):1239-76. DOI: 10.1081/STA-12003014810.1081/STA-120030148Search in Google Scholar

21. Der G, Everitt B. Statistical Analysis of Medical Data Using SAS. Boca Raton, Fl. Chapman Hall/CRC Press, 2005:1-440.10.1201/9781420057225Search in Google Scholar

22. Lee M, Saver JL, Towfighi A, Chow J, Ovbiagele B. Efficacy of fibrates for cardiovascular risk reduction in persons with atherogenic dyslipidemia: A meta-analysis Atherosclerosis. 2011;217(2):492-8.Search in Google Scholar

23. Zandbergen F, Plutzky J. PPARα in atherosclerosis and inflammation. Biochim Biophys Acta. 2007;1771(8):972-82. DOI: 10.1016/j. bbalip.2007.04.021Search in Google Scholar

24. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N. Engl. J. Med. 2005; 352(16):1685-95. DOI: 10.1056/NEJMra04343010.1056/NEJMra04343015843671Search in Google Scholar

25. Wu D, Molofsky AB, Liang HE, Ricardo-Gonzales RR, Jouihan HA, Bando JK et al. Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science. 2011;332(6026):243-47. DOI: 10.1126/science.120147510.1126/science.1201475314416021436399Search in Google Scholar

26. Lee BC, Lee J. Cellular and molecular players in adipose tissue inflammation in the development of obesity-induced insulin resistance. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 2014;1842(3):446-62. DOI: 10.1016/j.bbadis.2013.05.01710.1016/j.bbadis.2013.05.017380025323707515Search in Google Scholar

27. Jacobsen E, Helmers R, Lee J, Lee N. The expanding role(s) of eosinophils in health and disease. Blood. 2012;120(19):3882-90. DOI: 10.1182/ blood-2012-06-33084510.1182/blood-2012-06-330845Search in Google Scholar

28. Woerly G, Honda K, Loyens M,. Papin J P, Auwerx J, Staels B et al. Peroxisome proliferator-activated receptors alpha and gamma down-regulate allergic inflammation and eosinophil activation. J Exp Med. 2003;198(3):411-21. DOI: 10.1084/jem.2002138410.1084/jem.20021384Search in Google Scholar

29. D’Amore S, Vacca M, Graziano G, D’Orazio A, Cariello M, Martelli N et al. Nuclear receptors expression chart in peripheral blood mononuclear cells identifies patients with Metabolic Syndrome. Biochim Biophys Acta. 2013;1832(12):2289-301. DOI: 10.1016/j.bbadis.2013.09.00610.1016/j.bbadis.2013.09.006Search in Google Scholar

30. Faiola B, Peterson RA, Bordelon R, Brodie TA, Cummings CA, Romach EH et al. PPAR alpha, more than PPAR delta, Mediates the Hepatic and Skeletal Muscle Alterations Induced by the PPAR Agonist GW0742.Toxicol. Sci. 2008;105(2):384-94. DOI: 10.1093/toxsci/ kfn130Search in Google Scholar

31. Kim CS, Park HS, Kawada T, Kim J-H, Lim D, Hubbard NE et al. Circulating levels of MCP-1 and IL-8 are elevated in human obese subjects and associated with obesity related parameters. International Journal of Obesity. 2006;30(9):1347-55. DOI: 10.1038/ sj.ijo.080325910.1038/sj.ijo.0803259Search in Google Scholar

32. Pasceri V, Chang J, Willerson J, Yeh ETH. Modulation of C-Reactive Protein-Mediated Monocyte Chemoattractant Protein-1 Induction in Human Endothelial Cells by Anti Atherosclerosis Drugs. Circulation. 2001;103(21):2531-4. DOI: 10.1161/01.CIR.103.21.253110.1161/01.CIR.103.21.2531Search in Google Scholar

33. Dragomir E, Tircol M, Manduteanu I, Voinea M, Simionescu M. Aspirin and PPAR-alpha activators inhibit monocyte chemoattractant protein-1 expression induced by high glucose concentration in human endothelial cells. Vascul Pharmacol. 2006;44(6):440-9. DOI: 10.1016/j.vph.2006.02.00610.1016/j.vph.2006.02.006Search in Google Scholar

34. Christiansen T, Richelsen B and Bruun JM. Monocyte chemoattractant protein-1 is produced in isolated adi pocytes, associated with adiposity and reduced after weight loss in morbid obese subjects. International Journal of Obesity. 2005;29(1):146-50. DOI: 10.1038/ sj.ijo.080283910.1038/sj.ijo.0802839Search in Google Scholar

35. Fu J, Gaetani S, Oveisi F, Verme JL, Serrano A. Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-α. Nature. 2003;425(6953):90-3. DOI: 10.1038/nature0192110.1038/nature01921Search in Google Scholar

36. Vohl MC, Lepage P, Gaudet D, Brewer CG, Bétard C, Perron P et al. Molecular scanning of the human PPARa gene: association of the L162v mutation with hyperapobetalipoproteinemia.Lipid Res. 2000;41(6):945-52.10.1016/S0022-2275(20)32037-XSearch in Google Scholar

37. Perreault M, Zulyniak MA, Badoud F, Stephenson S, Badawi A, Buchholz A et al. A distinct fatty acid profile underlies the reduced inflammatory state of metabolically healthy obese individuals. PLoSOne. 2014; 9(2):e88539. DOI: 10.1371/journal.pone.0088539. DOI: 10.1371/journal.pone.008853910.1371/journal.pone.0088539391977724520395Search in Google Scholar

38. Tsimihodimos V, Miltiadous G , Daskalopoulou SS, Mikhailidis DP, Elisaf MS. Fenofibrate: Metabolic and Pleiotropic Effects. Current Vascular Pharmacology, 2005; (1):87-98 DOI: 10.2174/157016105277394210.2174/157016105277394215638786Search in Google Scholar

39. Wilson J, Duan R, El-Marakby A, Alhashim A and Lee DL. Peroxisome Proliferator Activated Receptor-α Agonist Slows the Progression of Hypertension, Attenuates Plasma Interleukin-6 Levels and Renal Inflammatory Markers in Angiotensin II Infused Mice. PPAR Research.2012; DOI:10.1155/2012/645969. DOI: 10.1155/2012/64596910.1155/2012/645969340581822848208Search in Google Scholar

40. Han J. Hajjar DP, Febbraio M, Nicholson AC. Native and modified low density lipoproteins increase the functional expression of the macrophage class B scavenger receptor, CD36. J. Biol. Chem.1997;272(34):21654-9. DOI: 10.1074/jbc.272.34.2165410.1074/jbc.272.34.216549261189Search in Google Scholar

41. Gautam S, Banerjee M. The macrophage Ox- LDL receptor, CD36 and its association with type II diabetes mellitus. Molecular genetics and metabolism. 2011;10 (4):389-98. DOI: 10.1016/j. ymgme.2010.12.012 Search in Google Scholar

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