期刊论文详细信息
Journal of Translational Medicine
Altered serum levels of IL-33 in patients with advanced systolic chronic heart failure: correlation with oxidative stress
Li-Guang Zhu2  Wa-Li Zhu2  Jing-Feng Wang1  Jing-Ting Mai1  Yang-Xin Chen1  Shuang-Lun Xie1  Hai-Feng Zhang1 
[1] Department of Cardiology, Sun Yat-sen Memory hospital, Sun Yat-sen University, Guangzhou, China;Department of Cardiology, Institute of Cardiovascular Diseases, First Affiliated Hospital, Guangxi Medical University, Nanning, China
关键词: Oxidative stress;    Soluble ST2;    Interleukin-33;    Chronic heart failure;   
Others  :  1205961
DOI  :  10.1186/1479-5876-10-120
 received in 2012-02-29, accepted in 2012-05-04,  发布年份 2012
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【 摘 要 】

Background

Interleukin-33 (IL-33) has been linked to chronic heart failure (CHF) in animal studies, but data on serum IL-33 levels in human CHF are not available. We analyzed levels of IL-33 in serum, and investigated the possible role of IL-33 in oxidative stress.

Methods

A total of 191 subjects with advanced systolic CHF (CHF group), 175 patients with pre-existing cardiac diseases but no CHF (non-CHF group), and 177 healthy controls (HC group) were enrolled. Serum levels of IL-33, soluble ST2 (sST2) and N-terminal-pro-brain natriuretic peptide (NT-proBNP), malondialdehyde (MDA) content, erythrocyte superoxide dismutase (eSOD) activity, as well as left ventricular ejection fraction (LVEF), were determined. The exact form of IL-33 in serum was identified. Effects of IL-33 and sST2 on MDA content and SOD activity in angiotensin (Ang II)-stimulated AC16 cells were assessed.

Results

Serum levels of IL-33 and sST2 were elevated in CHF patients, whereas IL-33/sST2 ratios were decreased. In CHF patients, pre-existing cardiac diseases and medications used upon hospital admission did not affect IL-33 concentrations or the IL-33/sST2 ratio. Full-length IL-33, which could not be detected in serum from HC and barely detected in non-CHF patients, was significantly up-regulated in CHF patients. IL-33 levels were positively correlated with markers of CHF severity. IL-33/sST2 ratios were slightly and negatively related to MDA concentrations. IL-33 directly reduced MDA and enhanced SOD activity in Ang II-stimulated AC16 cells, which were greatly attenuated by sST2.

Conclusions

Serum levels of IL-33, especially the full-length form, were elevated in CHF patients whereas IL-33 bioactivity was reduced. In advanced CHF, IL-33 may exert anti-oxidation effects, which may be overwhelmed by concurrently elevated levels of sST2.

【 授权许可】

   
2012 Zhang et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Krum H, Abraham WT: Heart failure. Lancet 2009, 373:941-955.
  • [2]Redfield MM, Jacobsen SJ, Burnett JC Jr, Mahoney DW, Bailey KR, Rodeheffer RJ: Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA 2003, 289:194-202.
  • [3]Seddon M, Looi YH, Shah AM: Oxidative stress and redox signalling in cardiac hypertrophy and heart failure. Heart 2007, 93:903-907.
  • [4]Fragasso G, Palloshi A, Puccetti P, Silipigni C, Rossodivita A, Pala M, Calori G, Alfieri O, Margonato A: A randomized clinical trial of trimetazidine, a partial free fatty acid oxidation inhibitor, in patients with heart failure. J Am Coll Cardiol 2006, 48:992-998.
  • [5]Liew FY, Pitman NI, McInnes IB: Disease-associated functions of IL-33: the new kid in the IL-1 family. Nat Rev Immunol 2010, 10:103-110.
  • [6]Kunes P, Holubcova Z, Kolackova M, Krejsek J: Interleukin-33, a novel member of the IL-1/IL-18 cytokine family, in cardiology and cardiac surgery. Thorac Cardiovasc Surg 2010, 58:443-449.
  • [7]Iwahana H, Yanagisawa K, Ito-Kosaka A, Kuroiwa K, Tago K, Komatsu N, Katashima R, Itakura M, Tominaga S: Different promoter usage and multiple transcription initiation sites of the interleukin-1 receptor-related human ST2 gene in UT-7 and TM12 cells. Eur J Biochem 1999, 264:397-406.
  • [8]Sanada S, Hakuno D, Higgins LJ, Schreiter ER, McKenzie AN, Lee RT: IL-33 and ST2 comprise a critical biomechanically induced and cardioprotective signaling system. J Clin Invest 2007, 117:1538-1549.
  • [9]Pascual-Figal DA, Ordonez-Llanos J, Tornel PL, Vazquez R, Puig T, Valdes M, Cinca J, de Luna AB, Bayes-Genis A: Soluble ST2 for predicting sudden cardiac death in patients with chronic heart failure and left ventricular systolic dysfunction. J Am Coll Cardiol 2009, 54:2174-2179.
  • [10]Weinberg EO, Shimpo M, Hurwitz S, Tominaga S, Rouleau JL, Lee RT: Identification of serum soluble ST2 receptor as a novel heart failure biomarker. Circulation 2003, 107:721-726.
  • [11]Reddy VS, Prabhu SD, Mummidi S, Valente AJ, Venkatesan B, Shanmugam P, Delafontaine P, Chandrasekar B: Interleukin-18 induces EMMPRIN expression in primary cardiomyocytes via JNK/Sp1 signaling and MMP-9 in part via EMMPRIN and through AP-1 and NF-kappaB activation. Am J Physiol Heart Circ Physiol 2010, 299:H1242-H1254.
  • [12]Seki K, Sanada S, Kudinova AY, Steinhauser ML, Handa V, Gannon J, Lee RT: Interleukin-33 prevents apoptosis and improves survival after experimental myocardial infarction through ST2 signaling. Circ Heart Fail 2009, 2:684-691.
  • [13]Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, Jessup M, Konstam MA, Mancini DM, Michl K, et al.: 2009 focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation 2009, 119:e391-479.
  • [14]Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG, Jessup M, Konstam MA, Mancini DM, Michl K, et al.: ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society. Circulation 2005, 112:e154-235.
  • [15]von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP: The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Epidemiology 2007, 18:800-804.
  • [16]Davidson MM, Nesti C, Palenzuela L, Walker WF, Hernandez E, Protas L, Hirano M, Isaac ND: Novel cell lines derived from adult human ventricular cardiomyocytes. J Mol Cell Cardiol 2005, 39:133-147.
  • [17]Pastorelli L, Garg RR, Hoang SB, Spina L, Mattioli B, Scarpa M, Fiocchi C, Vecchi M, Pizarro TT: Epithelial-derived IL-33 and its receptor ST2 are dysregulated in ulcerative colitis and in experimental Th1/Th2 driven enteritis. Proc Natl Acad Sci U S A 2010, 107:8017-8022.
  • [18]Castro P, Vukasovic JL, Chiong M, Diaz-Araya G, Alcaino H, Copaja M, Valenzuela R, Greig D, Perez O, Corbalan R, et al.: Effects of carvedilol on oxidative stress and chronotropic response to exercise in patients with chronic heart failure. Eur J Heart Fail 2005, 7:1033-1039.
  • [19]Nie F, Zhang X, Qi Q, Yang L, Yang Y, Liu W, Lu N, Wu Z, You Q, Guo Q: Reactive oxygen species accumulation contributes to gambogic acid-induced apoptosis in human hepatoma SMMC-7721 cells. Toxicology 2009, 260:60-67.
  • [20]Larsson T, Nisbeth U, Ljunggren O, Jüppner H, Jonsson KB: Circulating concentration of FGF-23 increases as renal function declines in patients with chronic kidney disease, but does not change in response to variation in phosphate intake in healthy volunteers. Kidney Int 2003, 64:2272-2279.
  • [21]Ohno T, Oboki K, Kajiwara N, Morii E, Aozasa K, Flavell RA, Okumura K, Saito H, Nakae S: Caspase-1, caspase-8, and calpain are dispensable for IL-33 release by macrophages. J Immunol 2009, 183:7890-7897.
  • [22]Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK, Zurawski G, Moshrefi M, Qin J, Li X, et al.: IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity 2005, 23:479-490.
  • [23]Cayrol C, Girard JP: The IL-1-like cytokine IL-33 is inactivated after maturation by caspase-1. Proc Natl Acad Sci U S A 2009, 106:9021-9026.
  • [24]May LT, Ndubuisi MI, Patel K, García D: Interleukin-6 chaperones in blood. Ann N Y Acad Sci 1995, 762:120-128.
  • [25]Dhillon OS, Narayan HK, Quinn PA, Squire IB, Davies JE, Ng LL: Interleukin 33 and ST2 in non-ST-elevation myocardial infarction: comparison with global registry of acute coronary events risk scoring and NT-proBNP. Am Heart J 2011, 161:1163-1170.
  • [26]Zhao W, Hu Z: The enigmatic processing and secretion of interleukin-33. Cell Mol Immunol 2010, 4:260-262.
  • [27]Bartunek J, Delrue L, Van Durme F, Muller O, Casselman F, De Wiest B, Croes R, Verstreken S, Goethals M, de Raedt H, et al.: Nonmyocardial production of ST2 protein in human hypertrophy and failure is related to diastolic load. J Am Coll Cardiol 2008, 52:2166-2174.
  • [28]Mok MY, Huang FP, Ip WK, Lo Y, Wong FY, Chan EY, Lam KF, Xu D: Serum levels of IL-33 and soluble ST2 and their association with disease activity in systemic lupus erythematosus. Rheumatology (Oxford) 2010, 49:520-527.
  • [29]Mu R, Huang HQ, Li YH, Li C, Ye H, Li ZG: Elevated serum interleukin 33 is associated with autoantibody production in patients with rheumatoid arthritis. J Rheumatol 2010, 37:2006-2013.
  • [30]Hong YS, Moon SJ, Joo YB, Jeon CH, Cho ML, Ju JH, Oh HJ, Heo YJ, Park SH: Measurement of interleukin-33 (IL-33) and IL-33 receptors (sST2 and ST2L) in patients with rheumatoid arthritis. J Korean Med Sci 2011, 26:1132-1139.
  • [31]Kakkar R, Hei H, Dobner S, Lee RT: Interleukin 33 as a mechanically responsive cytokine secreted by living cells. J Biol Chem 2012, 9:6941-6948.
  • [32]Chong AY, Blann AD, Patel J, Freestone B, Hughes E, Lip GY: Endothelial dysfunction and damage in congestive heart failure: relation of flow-mediated dilation to circulating endothelial cells, plasma indexes of endothelial damage, and brain natriuretic peptide. Circulation 2004, 110:1794-1798.
  • [33]Manzano-Fernandez S, Mueller T, Pascual-Figal D, Truong QA, Januzzi JL: Usefulness of soluble concentrations of interleukin family member ST2 as predictor of mortality in patients with acutely decompensated heart failure relative to left ventricular ejection fraction. Am J Cardiol 2011, 107:259-267.
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