DOI QR코드

DOI QR Code

Spatial and Temporal Expression, and Statin Responsiveness of Galectin-1 and Galectin-3 in Murine Atherosclerosis

  • Lee, Yong-Jin (Cardiovascular Research Center, Seoul St. Mary's Hospital) ;
  • Koh, Yoon-Seok (Cardiovascular Research Center, Seoul St. Mary's Hospital) ;
  • Park, Hyo Eun (Cardiovascular Research Center, Seoul St. Mary's Hospital) ;
  • Lee, Hee Jung (Cardiovascular Research Center, Seoul St. Mary's Hospital) ;
  • Hwang, Byung-Hee (Cardiovascular Research Center, Seoul St. Mary's Hospital) ;
  • Kang, Min-Kyu (Cardiovascular Research Center, Seoul St. Mary's Hospital) ;
  • Lee, So-Young (Cardiovascular Research Center, Seoul St. Mary's Hospital) ;
  • Kim, Pum-Joon (Cardiovascular Research Center, Seoul St. Mary's Hospital) ;
  • Ihm, Sang-Hyun (Cardiovascular Research Center, Seoul St. Mary's Hospital) ;
  • Seung, Ki-Bae (Cardiovascular Research Center, Seoul St. Mary's Hospital) ;
  • Chang, Kiyuk (Cardiovascular Research Center, Seoul St. Mary's Hospital)
  • Published : 2013.04.30

Abstract

Background and Objectives: Existing data on the spatiotemporal expression patterns of a variety of galectins in murine atherosclerosis are limited. We investigated the expression levels of galectins, and their in vivo spatiotemporal expression patterns and statin responsiveness in the inflamed atherosclerotic plaques of apolipoprotein E $(apoE)^{-/-}$ mice. Materials and Methods: Galectins expression patterns in aortic atherosclerotic plaques and serum galectin-3 levels were investigated in 26-week-old $apoE^{-/-}$ (n=6) and C57BL/6 mice (n=9). To investigate the spatial and temporal patterns of galectin-1 and galectin-3 in plaques, high-cholesterol diet-fed 26-week-old (n=12) and 36-week-old $apoE^{-/-}$ mice (n=6) were sacrificed and their aortas were examined for galectins' expression using immunoblot analysis and immunohistochemical stain. 36-week-old $apoE^{-/-}$ mice were treated with atorvastatin (n=3, 0.57 mg/kg/day) for the evaluation of its effect on aortic galectins' expression. Results: Immunoblot analyses showed that galectin-1 and galectin-3 were the predominant galectins expressed in murine atherosclerosis. The serum galectin-3 level was significantly higher in $apoE^{-/-}$ mice (p<0.001). While galectin-1 was weakly expressed in both intimal plaques and the media of atherosclerotic aortas, galectin-3 was heavily and exclusively accumulated in intimal plaques. Galectin-3 distribution was colocalized with plaque macrophages' distribution (r=0.66). As the degree of plaque extent and inflammation increased, the intraplaque galectin-3 expression levels proportionally elevated (p<0.01 vs. baseline), whereas galectin-1 expression had not elevated (p=0.14 vs. baseline). Atorvastatin treatment markedly reduced intraplaque galectin-3 and macrophage signals (p<0.001 vs. baseline), whereas it failed to reduce galectin-1 expression in the aortas. Conclusion: Galectin-3 is the predominant gal and is colocalized with macrophages within atherosclerotic plaques. Intraplaque galectin-3 expression reflects the degree of plaque inflammation.

Keywords

References

  1. Libby P, Ridker PM, Hansson GK; Leducq Transatlantic Network on Atherothrombosis. Inflammation in atherosclerosis: from pathophysiology to practice. J Am Coll Cardiol 2009;54:2129-38. https://doi.org/10.1016/j.jacc.2009.09.009
  2. Almkvist J, Karlsson A. Galectins as inflammatory mediators. Glycoconj J 2004;19:575-81.
  3. Rubinstein N, Ilarregui JM, Toscano MA, Rabinovich GA. The role of galectins in the initiation, amplification and resolution of the inflammatory response. Tissue Antigens 2004;64:1-12. https://doi.org/10.1111/j.0001-2815.2004.00278.x
  4. Zanetta JP, Badache A, Maschke S, Marschal P, Kuchler S. Carbohydrates and soluble lectins in the regulation of cell adhesion and proliferation. Histol Histopathol 1994;9:385-412.
  5. Rabinovich GA, Toscano MA, Ilarregui JM, Rubinstein N. Shedding light on the immunomodulatory properties of galectins: novel regulators of innate and adaptive immune responses. Glycoconj J 2004;19:565-73.
  6. Moiseeva EP, Javed Q, Spring EL, de Bono DP. Galectin 1 is involved in vascular smooth muscle cell proliferation. Cardiovasc Res 2000;45:493-502. https://doi.org/10.1016/S0008-6363(99)00276-X
  7. Hughes RC. Secretion of the galectin family of mammalian carbohydrate-binding proteins. Biochim Biophys Acta 1999;1473:172-85. https://doi.org/10.1016/S0304-4165(99)00177-4
  8. Sano H, Hsu DK, Yu L, et al. Human galectin-3 is a novel chemoattractant for monocytes and macrophages. J Immunol 2000;165:2156-64. https://doi.org/10.4049/jimmunol.165.4.2156
  9. Iacobini C, Menini S, Ricci C, et al. Accelerated lipid-induced atherogenesis in galectin-3-deficient mice: role of lipoxidation via receptormediated mechanisms. Arterioscler Thromb Vasc Biol 2009;29:831-6. https://doi.org/10.1161/ATVBAHA.109.186791
  10. Falcone C, Lucibello S, Mazzucchelli I, et al. Galectin-3 plasma levels and coronary artery disease: a new possible biomarker of acute coronary syndrome. Int J Immunopathol Pharmacol 2011;24:905-13. https://doi.org/10.1177/039463201102400409
  11. Kircher MF, Grimm J, Swirski FK, et al. Noninvasive in vivo imaging of monocyte trafficking to atherosclerotic lesions. Circulation 2008;117:388-95. https://doi.org/10.1161/CIRCULATIONAHA.107.719765
  12. Rabinovich GA, Baum LG, Tinari N, et al. Galectins and their ligands: amplifiers, silencers or tuners of the inflammatory response? Trends Immunol 2002;23:313-20. https://doi.org/10.1016/S1471-4906(02)02232-9
  13. Chen HY, Fermin A, Vardhana S, et al. Galectin-3 negatively regulates TCR-mediated CD4+ T-cell activation at the immunological synapse. Proc Natl Acad Sci U S A 2009;106:14496-501. https://doi.org/10.1073/pnas.0903497106
  14. MacKinnon AC, Farnworth SL, Hodkinson PS, et al. Regulation of alternative macrophage activation by galectin-3. J Immunol 2008;180:2650-8. https://doi.org/10.4049/jimmunol.180.4.2650
  15. Jeon SB, Yoon HJ, Chang CY, Koh HS, Jeon SH, Park EJ. Galectin-3 exerts cytokine-like regulatory actions through the JAK-STAT pathway. J Immunol 2010;185:7037-46. https://doi.org/10.4049/jimmunol.1000154
  16. Forsman H, Islander U, Andreasson E, et al. Galectin 3 aggravates joint inflammation and destruction in antigen-induced arthritis. Arthritis Rheum 2011;63:445-54. https://doi.org/10.1002/art.30118
  17. Nachtigal M, Al-Assaad Z, Mayer EP, Kim K, Monsigny M. Galectin-3 expression in human atherosclerotic lesions. Am J Pathol 1998;152:1199-208.
  18. Ozaki K, Inoue K, Sato H, et al. Functional variation in LGALS2 confers risk of myocardial infarction and regulates lymphotoxin-alpha secretion in vitro. Nature 2004;429:72-5. https://doi.org/10.1038/nature02502
  19. Chellan B, Narayani J, Appukuttan PS. Galectin-1, an endogenous lectin produced by arterial cells, binds lipoprotein(a) [Lp(a)] in situ: relevance to atherogenesis. Exp Mol Pathol 2007;83:399-404. https://doi.org/10.1016/j.yexmp.2007.04.004
  20. Nachtigal M, Ghaffar A, Mayer EP. Galectin-3 gene inactivation reduces atherosclerotic lesions and adventitial inflammation in ApoE-deficient mice. Am J Pathol 2008;172:247-55. https://doi.org/10.2353/ajpath.2008.070348
  21. Khallou-Laschet J, Varthaman A, Fornasa G, et al. Macrophage plasticity in experimental atherosclerosis. PLoS One 2010;5:e8852. https://doi.org/10.1371/journal.pone.0008852
  22. Liu FT, Rabinovich GA. Galectins: regulators of acute and chronic inflammation. Ann N Y Acad Sci 2010;1183:158-82. https://doi.org/10.1111/j.1749-6632.2009.05131.x
  23. Romaniuk MA, Tribulatti MV, Cattaneo V, et al. Human platelets express and are activated by galectin-8. Biochem J 2010;432:535-47. https://doi.org/10.1042/BJ20100538
  24. Liu FT, Yang RY, Hsu DK. Galectins in acute and chronic inflammation. Ann N Y Acad Sci 2012;1253:80-91. https://doi.org/10.1111/j.1749-6632.2011.06386.x
  25. Arar C, Gaudin JC, Capron L, Legrand A. Galectin-3 gene (LGALS3) expression in experimental atherosclerosis and cultured smooth muscle cells. FEBS Lett 1998;430:307-11. https://doi.org/10.1016/S0014-5793(98)00683-8
  26. Moiseeva EP, Williams B, Samani NJ. Galectin 1 inhibits incorporation of vitronectin and chondroitin sulfate B into the extracellular matrix of human vascular smooth muscle cells. Biochim Biophys Acta 2003;1619:125-32. https://doi.org/10.1016/S0304-4165(02)00447-6
  27. Liu FT, Hsu DK, Zuberi RI, Kuwabara I, Chi EY, Henderson WR Jr. Expression and function of galectin-3, a beta-galactoside-binding lectin, in human monocytes and macrophages. Am J Pathol 1995;147:1016-28.
  28. Puato M, Faggin E, Rattazzi M, et al. Atorvastatin reduces macrophage accumulation in atherosclerotic plaques: a comparison of a nonstatinbased regimen in patients undergoing carotid endarterectomy. Stroke 2010;41:1163-8. https://doi.org/10.1161/STROKEAHA.110.580811

Cited by

  1. Effects of 12 weeks of atorvastatin therapy on myocardial fibrosis and circulating fibrosis biomarkers in statin-naive patients with hypertension with atherosclerosis vol.64, pp.7, 2013, https://doi.org/10.1136/jim-2016-000092
  2. Galectin-1 as an Emerging Mediator of Cardiovascular Inflammation: Mechanisms and Therapeutic Opportunities vol.2018, pp.None, 2018, https://doi.org/10.1155/2018/8696543
  3. Serum Galectin-3 and Poor Outcomes Among Patients With Acute Ischemic Stroke vol.49, pp.1, 2013, https://doi.org/10.1161/strokeaha.117.019084
  4. Therapeutic effects of simvastatin on Galectin-3 and oxidative stress parameters in endotoxemic lung tissue vol.38, pp.3, 2013, https://doi.org/10.1042/bsr20180308
  5. Galectin-1 Restricts Vascular Smooth Muscle Cell Motility Via Modulating Adhesion Force and Focal Adhesion Dynamics vol.8, pp.None, 2013, https://doi.org/10.1038/s41598-018-29843-3
  6. Galectin-3 Is a Potential Mediator for Atherosclerosis vol.2020, pp.None, 2013, https://doi.org/10.1155/2020/5284728
  7. Galectin-3 as the Prognostic Factor of Adverse Cardiovascular Events in Long-Term Follow up in Patients after Myocardial Infarction—A Pilot Study vol.9, pp.6, 2020, https://doi.org/10.3390/jcm9061640
  8. Value of Galectin-3 in Acute Myocardial Infarction vol.20, pp.4, 2013, https://doi.org/10.1007/s40256-019-00387-9
  9. Galectin-1 is associated with the severity of coronary artery disease and adverse cardiovascular events in patients undergoing coronary angiography vol.10, pp.1, 2020, https://doi.org/10.1038/s41598-020-77804-6
  10. The Diagnostic and Therapeutic Potential of Galectin-3 in Cardiovascular Diseases vol.12, pp.1, 2022, https://doi.org/10.3390/biom12010046