Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1
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ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2014, vol. 23, nr 5, September-October, p. 723–728

Publication type: original article

Language: English

Serum Proinflammatory Chemokines in Healthy Elderly Taking or not Taking Simvastatin – Data from the Brisighella Heart Study

Sergio D’Addato1,A,F, Arrigo F. G. Cicero1,C,D,F, Martina Rosticci1,B,F, Alessandra Reggi1,D,F, Sandra Cristino2,B,F, Ada Dormi1,C,F, Claudio Borghi1,E,F

1 Medicine and Surgery Sciences Department, University of Bologna, Italy

2 Biological, Geological and Environmental Sciences Deptartment, University of Bologna, Italy

Abstract

Background. Recent preclinical evidence and data from adult subjects suggests that statins could improve the proinflammatory profile of hypercholesterolemic subjects.
Objectives. We aim to compare the serum levels of a set of proinflammatory chemokines in elderly statistical twins taking or not taking statins.
Material and Methods. Among the historical cohort of the Brisighella Heart Study, we chose 40 healthy elderly subjects continuously treated with statins for at least 1 year and 40 cross-matched subjects not treated with statins (M : F = 1 : 1) characterized by similar age, body mass index (BMI), leisure-time and working activity, smoking habits, history of cardiovascular disease, systolic and diastolic blood pressure, fasting plasma glucose, plasma lipids, uric acid, and creatinine.
Results. The proinflammatory chemokine serum level is similar in statin untreated and treated statistical twins. The OR to have a serum level of monocyte chemoattractant protein (MCP-1) lower than the 50th percentile of the distribution in statin-treated subjects compared to the statin untreated subjects is 0.669 (95% CI 0.193; 2.327), the OR for interleukin-8 (IL-8) = 0.818 (95% CI 0.236; 2.835), the OR for γ-interferon inducible protein-10 (IP-10) = 1.361 (95% CI 0.358; 5.175), and for interleukin-18 (IL-18) = 0.545 (95% CI 0.155; 1.914).
Conclusion. In relatively healthy, elderly subjects selected from a randomized general population sample, we did not observe differences in the serum levels of the selected set of proinflammatory chemokines in statin treated and untreated subjects with similar LDL-C level, suggesting that cholesterol reduction per se could be a main determinant of statin anti-inflammatory effects.

Key words

chemokines, interleukin-8, interleukin-18, monocyte chemoattractant protein, statins.

References (29)

  1. Wang JC, Bennett M: Aging and atherosclerosis: mechanisms, functional consequences, and potential therapeutics for cellular senescence. Circ Res 2012, 111, 245–259.
  2. Moore KJ, Tabas I: Macrophages in the pathogenesis of atherosclerosis. Cell 2011, 145, 341–355.
  3. Shah PK: Inflammation and plaque vulnerability. Cardiovasc Drugs Ther 2009, 23, 31–40.
  4. Campbell KA, Lipinski MJ, Doran AC, Skaflen MD, Fuster V, McNamara CA: Lymphocytes and the adventitial immune response in atherosclerosis. Circ Res 2012, 110, 889–900.
  5. Halvorsen B, Lund Sagen E, Ueland T, Aukrust P, Tonstad S: Effect of smoking cessation on markers of inflammation and endothelial cell activation among individuals with high risk for cardiovascular disease. Scand J Clin Lab Invest 2007, 67, 604–611.
  6. Antonelli A, Fallahi P, Ferrari SM, Ghiadoni L, Virdis A, Mancusi C, Centanni M, Taddei S, Ferrannini E: High serum levels of CXC (CXCL10) and CC (CCL2) chemokines in untreated essential hypertension. Int J Immunopathol Pharmacol 2012, 25, 387–395.
  7. Gutierrez DA, Puglisi MJ, Hasty AH: Impact of increased adipose tissue mass on inflammation, insulin resistance, and dyslipidemia. Curr Diab Rep 2009, 9, 26–32.
  8. Rull A, Camps J, Alonso-Villaverde C, Joven J: Insulin resistance, inflammation, and obesity: role of monocyte chemoattractant protein-1 (or CCL2) in the regulation of metabolism. Mediators Inflamm 2010, 2010. Pii: 326580.
  9. Yadav A, Saini V, Arora S: MCP-1: chemoattractant with a role beyond immunity: a review. Clin Chim Acta 2012, 411, 1570–1579.
  10. Shantsila E, Lip GY: Monocytes in acute coronary syndromes. Arterioscler Thromb Vasc Biol 2009, 29, 1433–1438.
  11. Gustafson B: Adipose tissue, inflammation and atherosclerosis. J Atheroscler Thromb 2010, 17, 332–341.
  12. Valente AJ, Yoshida T, Murthy SN, Sakamuri SS, Katsuyama M, Clark RA, Delafontaine P, Chandrasekar B: Angiotensin-II enhances AT1-Nox1 binding, and stimulates arterial smooth muscle cell migration and proliferation through AT1, Nox1, and interleukin-18. Am J Physiol Heart Circ Physiol 2012. [Ahead of print]
  13. Trøseida M, Lappegardab KT, Mollnes TE, Arnesen H, Seljeflot I: The effect of exercise on serum levels of interleukin-18 and components of the metabolic syndrome. Metab Syndr Relat Disord 2009, 7, 579–584.
  14. Nomura S, Shouzu A, Omoto S, Inami N, Shimazu T, Satoh D, Kajuyra T, Yamada K, Urase F, Maeda Y, Iwasaka T: Effects of pitavastatin on monocyte chemoattractant protein-1 in hyperlipidemic patients. Blood Coagul Fibrinolysis 2009, 20, 440–447.
  15. Krysiak R, Gdula-Dymek A, Scieszka J, Okopien B: Anti-inflammatory and monocyte-suppressing effects of simvastatin in patients with impaired fasting glucose. Basic Clin Pharmacol Toxicol 2011, 108, 131–137.
  16. Cicero AF, Salvi P, D’Addato S, Rosticci M, Borghi C: Association between serum uric acid, hypertension, vascular stiffness and subclinical atherosclerosis: data from the Brisighella Heart Study. J Hypertens 2014, 32, 57–64.
  17. Cicero AFG, D’Addato S, Santi F, Ferroni A, Borghi C: Leisure-time physical activity and cardiovascular disease mortality: the Brisighella Heart Study. J Cardiovasc Med 2012, 13, 559–564.
  18. Leng XS: Multiplex technologies for cytokine measurement in inflammation and aging research. J Gerontol A Biol Sci Med Sci 2008, 63, 879–884.
  19. Miles EA, Rees D, Banerjee T, Cazzola R, Lewis S, Wood R, Oates R, Tallant A, Cestaro B, Yagoob P, Whale KW, Calder PC: Age-related increases in circulating inflammatory markers in men are independent of BMI, blood pressure and blood lipid concentrations. Atherosclerosis 2008, 196, 298–305.
  20. Ognjanovic S, Jacobs DR, Steinberger J, Moran A, Sinaiko AR: Relation of chemokines to BMI and insulin resistance at ages 18–21. Int J Obes 2012 Apr 17. Doi: 10.1038/ijo.2012.61.1 [Epub ahead of print]
  21. Rodondi N, Marques-Vidal P, Butler J, Sutton-Tyrrell K, Cornuz J, Satterfield S, Harris T, Bauer DC, Ferrucci L, Vittinghoff E, Newman AB: Markers of Atherosclerosis and Inflammation for Prediction of Coronary Heart Disease in Older Adults. Am J Epidemiol 2010, 171, 540–549.
  22. Lardizabal JA, Deedwania PC: The anti-ischemic and anti-anginal properties of statins. Curr Atheroscler Rep 2011, 13, 43–50.
  23. Olivieri F, Mazzanti I, Abbatecola AM, Recchioni R, Marcheselli F, Procopio AD, Antonicelli R: Telomere/ Telomerase system: a new target of statins pleiotropic effect? Curr Vasc Pharmacol 2012, 10, 216–224.
  24. Ropponen JO, Syrjälä SO, Hollmén M, Tuuminen R, Krebs R, Keränen MA, Vaali K, Nykänen AI, Lemström KB, Tikkanen JM: Effect of simvastatin on development of obliterative air way disease: an experimental study. J Heart Lung Transplant 2012, 31, 194–203.
  25. Kinlay S: Low-density lipoprotein-dependent and -independent effects of cholesterol-lowering therapies on C-reactive protein: a meta-analysis. J Am Coll Cardiol 2007, 49, 2003–2009.
  26. McDermott DH, Yang Q, Kathiresan S, Cupples LA, Massaro JM, Keaney JF Jr, Larson MG, Vasan RS, Hirschhorn JN, O’Donnell CJ, Murphy PM, Benjamin EJ: CCL2 polymorphisms are associated with serum monocyte chemoattractant protein-1 levels and myocardial infarction in the Framingham Heart Study. Circulation 2005, 112, 1113–1120.
  27. Samnegård A, Hulthe J, Silveira A, Ericsson CG, Hamsten A, Eriksson P: Gender specific associations between matrix metalloproteinases and inflammatory markers in post myocardial infarction patients. Atherosclerosis 2009, 202, 550–556.
  28. Njemini R, Bautmans I, Lambert M, Demanet C, Mets T: Heat shock proteins and chemokine/cytokine secretion profile in ageing and inflammation. Mech Ageing Dev 2007, 128, 450–454.
  29. Mihos CG, Salas MJ, Santana O: The pleiotropic effects of the hydroxy-methyl-glutaryl-CoA reductase inhibitors in cardiovascular disease: a comprehensive review. Cardiol Rev 2010, 18, 298–304.