Summary
In various autoimmune diseases, Galecin-9 (Gal-9) has been shown to regulate the T-cell balance by decreasing Th1 and Th17, while increasing the number of regulatory T cells (Tregs). However, the role of Gal-9 in the patients with acute coronary syndrome (ACS) and chronic kidney disease (CKD) remains unclear. This study aims to measure the Gal-9 levels in serum and peripheral blood mononuclear cells (PBMCs) in patients with ACS plus CKD and examine their clinical implication. The serum levels of Gal-9 were determined by enzyme-linked immunosorbent assay (ELISA), the expression levels of Gal-9, Tim-3, and Foxp3 mRNA in PBMCs were detected by real-time reverse transcription-polymerase chain reaction (RT-PCR), and the expression of Gal-9 on the surface of PBMCs and in PBMCs was analyzed by flow cytometry. Furthermore, the correlation of serum Gal-9 levels with anthropometric and biochemical variables in patients with ACS plus CKD was analyzed. The lowest levels of Gal-9 in serum and PBMCs were found in the only ACS group, followed by the ACS+CKD group, and the normal coronary artery (NCA) group, respectively. Serum Gal-9 levels were increased along with the progression of glomerular filtration rate (GFR) categories of G1 to G4. Additionally, serum Gal-9 levels were negatively correlated with high-sensitivity C-reactive protein (hs-CRP), estimated GFR (eGFR), and lipoprotein(a), but positively with creatinine, age, osmotic pressure, and blood urea nitrogen (BUN). Notably, serum Gal-9 was independently associated with hs-CRP, osmotic pressure, and lipoprotein(a). Furthermore, serum Gal-9 levels were elevated in patients with type 2 diabetes (T2DM) and impaired glucose tolerance (IGT) in ACS group. It was suggested that the levels of Gal-9 in serum and PBMCs were decreased in patients with simple ACS and those with ACS plus CKD, and hs-CRP, eGFR, osmotic pressure and T2DM may have an influence on serum Gal-9 levels.
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References
Libby P. Inflammation in atherosclerosis. Arterioscler Thromb Vasc Biol, 2012,32(9):2045–2051
Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med, 2005,352:1685–1695
Hansson GK. Innate and Adaptive Immunity in the Pathogenesis of Atherosclerosis. Circ Res, 2002,91(4):281–291
Laurat E, Poirier B, Tupin E, et al. In vivo downregulation of T helper cell 1 immune responses reduces atherogenesis in apolipoprotein E-knockout mice. Circulation, 2001,104:197–202
Methe H, Brunner S, Wiegand D, et al. Enhanced T-helper-1 lymphocyte activation patterns in acute coronary syndromes. J Am Coll Cardiol, 2005,45(12):1939–1945
Cheng X, Liao YH, Ge H, et al. TH1/TH2 functional imbalance after acute myocardial infarction: coronary arterial inflammation or myocardial inflammation. J Clin Immunol, 2005,25(3):246–253
Cheng X, Yu X, Ding YJ, et al. The Th17/Treg imbalance in patients with acute coronary syndrome. Clin Immunol, 2008,127(1):89–97
Kishore U, Eggleton P, Reid KB, et al. Modular organization of carbohydrate recognition domains in animal lectins. Matrix Biology, 1997,15:583–592
Zhu C, Anderson AC, Schubart A, et al. The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat Immunol, 2005,6(12):1245–1252
Kashio Y, Nakamura K, Abedin MJ, et al. Galectin-9 induces apoptosis through the calcium-calpain-caspase-1 pathway. J Immunol, 2003,170(7):3631–3636
Wang F, Xu J, Liao Y, et al. Tim-3 ligand galectin-9 reduces IL-17 level and accelerates Klebsiella pneumoniae infection. Cell Immunol, 2011,269(1):22–28
Oomizu S, Arikawa T, Niki T, et al. Galectin-9 suppresses Th17 cell development in an IL-2-dependent but Tim-3-independent manner. Clin Immunol, 2012,143(1):51–58
Bi S, Earl LA, Jacobs L, et al. Structural features of galectin-9 and galectin-1 that determine distinct T cell death pathways. J Biol Chem, 2008,283(18):12 248–12 258
Wang F, Wan L, Zhang C, et al. Tim-3-Galectin-9 pathway involves the suppression induced by CD4+CD25+ regulatory T cells. Immunobiology, 2009,214(5):342–349
Seki M, Oomizu S, Sakata KM, et al. Galectin-9 suppresses the generation of Th17, promotes the induction of regulatory T cells, and regulates experimental autoimmune arthritis. Clin Immunol, 2008,127(1):78–88
Chou FC, Shieh SJ, Sytwu HK. Attenuation of Th1 response through galectin-9 and T-cell Ig mucin 3 interaction inhibits autoimmune diabetes in NOD mice. Eur J Immunol, 2009,39(9):2403–2411
Kanzaki M, Wada J, Sugiyama K, et al. Galectin-9 and T cell immunoglobulin mucin-3 pathway is a therapeutic target for type 1 diabetes. Endocrinology, 2012,153(2):612–620
Leitner J, Rieger A, Pickl WF, et al. TIM-3 does not act as a receptor for galectin-9. PLoS Pathog, 2013,9(3):e1003253
Vaitaitis GM, Wagner DH, Jr. Galectin-9 controls CD40 signaling through a Tim-3 independent mechanism and redirects the cytokine profile of pathogenic T cells in autoimmunity. PLoS One, 2012,7(6):e38708
Su EW, Bi S, Kane LP. Galectin-9 regulates T helper cell function independently of Tim-3. Glycobiology, 2011,21(10):1258–1265
Foks AC, Ran IA, Wasserman L, et al. T-cell immunoglobulin and mucin domain 3 acts as a negative regulator of atherosclerosis. Arterioscler Thromb Vasc Biol, 2013,33(11):2558–2565
Kurose Y, Wada J, Kanzaki M, et al. Serum galectin-9 levels are elevated in the patients with type 2 diabetes and chronic kidney disease. BMC Nephrology, 2013,14:23
Zhu R, Liu C, Tang H, et al. Serum Galectin-9 Levels Are Associated with Coronary Artery Disease in Chinese Individuals. Mediators Inflamm, 2015,2015:457167
Levey AS, de Jong PE, Coresh J, et al. The definition, classification, and prognosis of chronic kidney disease: a KDIGO Controversies Conference report. Kidney Int, 2011,80(1):17–28
Matsuo S, Imai E, Horio M, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis, 2009,53(6):982–992
Gotsman I, Grabie N, Gupta R, et al. Impaired regulatory T-cell response and enhanced atherosclerosis in the absence of inducible costimulatory molecule. Circulation, 2006,114(19):2047–2055
Mor A, Planer D, Luboshits G, et al. Role of naturally occurring CD4+ CD25+ regulatory T cells in experimental atherosclerosis. Arterioscler Thromb Vasc Biol, 2007,27(4):893–900
Xie JJ, Wang J, Tang TT, et al. The Th17/Treg functional imbalance during atherogenesis in ApoE(-/-) mice. Cytokine, 2010,49(2):185–193
Koguchi K, Anderson DE, Yang L, et al. Dysregulated T cell expression of TIM3 in multiple sclerosis. J Exp Med, 2006,203(6):1413–1418
Chabot SKY, Seki M, Shirato Y, et al. Regulation of galectin-9 expression and release in Jurkat T cell line cells. Glycobiology, 2002,12:111–118
Delacour D, Koch A, Jacob R. The role of galectins in protein trafficking. Traffic, 2009,10(10):1405–1413
Chirico WJ. C Protein release through nonlethal oncotic pores as an alternative nonclassical secretory pathway. BMC Cell Biol, 2011,12:46
Corson MA. Emerging inflammatory markers for assessing coronary heart disease risk. Current Cardiology Reports, 2009,11:452–459
Weber C, Noels H. Atherosclerosis: current pathogenesis and therapeutic options. Nat Med, 2011,17(11):1410–1422
Cheng XW, Kikuchi R, Ishii H, et al. Circulating cathepsin K as a potential novel biomarker of coronary artery disease. Atherosclerosis, 2013,228(1):211–216
Drakopoulou M, Toutouzas K, Stefanadi E, et al. Association of inflammatory markers with angiographic severity and extent of coronary artery disease. Atherosclerosis, 2009,206(2):335–339
Noren Hooten N, Ejiogu N, Zonderman AB, et al. Association of oxidative DNA damage and C-reactive protein in women at risk for cardiovascular disease. Arterioscler Thromb Vasc Biol, 2012,32(11):2776–2784
Arroyo-Espliguero R, Avanzas P, Cosin-Sales J, et al. C-reactive protein elevation and disease activity in patients with coronary artery disease. Eur Heart J, 2004,25(5):401–408
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The authors declare that there is no conflict of interests regarding the publication of this paper.
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This project was supported by grants from National Natural Science Foundation of China (No. 81270354) and Natural Science for Youth Foundation (No. 81300213).
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Xie, Jh., Zhu, Rr., Zhao, L. et al. Down-regulation and Clinical Implication of Galectin-9 Levels in Patients with Acute Coronary Syndrome and Chronic Kidney Disease. CURR MED SCI 40, 662–670 (2020). https://doi.org/10.1007/s11596-020-2238-5
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DOI: https://doi.org/10.1007/s11596-020-2238-5