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Dipeptidyl peptidases in atherosclerosis: expression and role in macrophage differentiation, activation and apoptosis

Basic Research in Cardiology volume 108, Article number: 350 (2013) Cite this article

Abstract

Atherosclerosis is a chronic inflammatory disorder of the arterial wall leading to coronary artery disease, stroke, and peripheral arterial disease. Along with the discovery of dipeptidyl peptidase 4 (DPP4) as a therapeutic target in type 2 diabetes, a role for DPP4 in atherosclerosis is emerging. However, until now the expression and role of other DPPs such as DPP8 and DPP9 in atherosclerosis is completely unknown. In the present study, we first investigated DPP expression in human atherosclerotic plaques. DPP4 could only be observed in endothelial cells of plaque neovessels in half of the specimens. In contrast, DPP8 and DPP9 were abundantly present in macrophage-rich regions of plaques. We then focused on DPP expression and function in macrophage differentiation, activation and apoptosis. DPP8/9 was responsible for most of the DPP activity in macrophages. During monocyte to macrophage differentiation, DPP9 was upregulated both in pro-inflammatory M1 (3.7 ± 0.3-fold increase) and anti-inflammatory M2 macrophages (3.7 ± 0.4-fold increase) whereas DPP8 expression remained unchanged. Inhibition of DPP8/9 activity with compound 1G244 reduced activation of M1 macrophages (IL-6 88 ± 16 vs. 146 ± 19 pg/ml; TNFα 3.8 ± 1.0 vs. 6.6 ± 1.9 ng/ml in treated vs. untreated cells), but not of M2 macrophages. Likewise, DPP9 silencing reduced TNFα and IL-6 secretion, pointing to a DPP9-mediated effect of the inhibitor. DPP8/9 inhibition also enhanced macrophage apoptosis (15 ± 4 vs. 7 ± 3 % in untreated cells). Because pro-inflammatory macrophages play a key role in atherogenesis, plaque rupture and subsequent infarction, DPP9 inhibition might provide interesting therapeutic prospects in reducing atherosclerosis and/or in the prevention of plaque rupture.

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Abbreviations

AV:

Annexin V

DPP:

Dipeptidyl peptidase

ECs:

Endothelial cells

GM-CSF:

Granulocyte macrophage-colony stimulating factor

M-CSF:

Macrophage-colony stimulating factor

MDMs:

Monocyte-derived macrophages

Mo:

Monocytes

Mφ:

Macrophages

NPY:

Neuropeptide Y

PI:

Propidium iodide

PBMCs:

Peripheral blood mononuclear cells

PMA:

Phorbol 12-myristate 13-acetate

SMCs:

Smooth muscle cells

References

  1. Abbott CA, Yu DM, Woollatt E, Sutherland GR, McCaughan GW, Gorrell MD (2000) Cloning, expression and chromosomal localization of a novel human dipeptidyl peptidase (DPP) IV homolog, DPP8. Eur J Biochem 267:6140–6150. doi:10.1046/j.1432-1327.2000.01617.x

    PubMed  Article  CAS  Google Scholar 

  2. Ajami K, Abbott CA, McCaughan GW, Gorrell MD (2004) Dipeptidyl peptidase 9 has two forms, a broad tissue distribution, cytoplasmic localization and DPIV-like peptidase activity. Biochim Biophys Acta 1679:18–28. doi:10.1016/j.bbaexp.2004.03.010

    PubMed  Article  CAS  Google Scholar 

  3. Ansorge S, Bank U, Heimburg A, Helmuth M, Koch G, Tadje J, Lendeckel U, Wolke C, Neubert K, Faust J, Fuchs P, Reinhold D, Thielitz A, Tager M (2009) Recent insights into the role of dipeptidyl aminopeptidase IV (DPIV) and aminopeptidase N (APN) families in immune functions. Clin Chem Lab Med 47:253–261. doi:10.1515/CCLM.2009.063

    PubMed  Article  CAS  Google Scholar 

  4. Arakawa M, Mita T, Azuma K, Ebato C, Goto H, Nomiyama T, Fujitani Y, Hirose T, Kawamori R, Watada H (2010) Inhibition of monocyte adhesion to endothelial cells and attenuation of atherosclerotic lesion by a glucagon-like peptide-1 receptor agonist, exendin-4. Diabetes 59:1030–1037. doi:10.2337/db09-1694

    PubMed  Article  CAS  Google Scholar 

  5. Bjelke JR, Christensen J, Nielsen PF, Branner S, Kanstrup AB, Wagtmann N, Rasmussen HB (2006) Dipeptidyl peptidases 8 and 9: specificity and molecular characterization compared with dipeptidyl peptidase IV. Biochem J 396:391–399. doi:10.1042/BJ20060079

    PubMed  Article  CAS  Google Scholar 

  6. Böyum A (1968) Isolation of mononuclear cells and granulocytes from human blood. Isolation of mononuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl 97:77–89

    PubMed  Google Scholar 

  7. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254. doi:10.1016/0003-2697(76)90527-3

    PubMed  Article  CAS  Google Scholar 

  8. Chrysant SG, Chrysant GS (2012) Clinical implications of cardiovascular preventing pleiotropic effects of dipeptidyl peptidase-4 inhibitors. Am J Cardiol 109:1681–1685. doi:10.1016/j.amjcard.2012.01.398

    PubMed  Article  CAS  Google Scholar 

  9. Croons V, Martinet W, Herman AG, Timmermans JP, De Meyer GR (2007) Selective clearance of macrophages in atherosclerotic plaques by the protein synthesis inhibitor cycloheximide. J Pharmacol Exp Ther 320:986–993. doi:10.1124/jpet.106.113944

    PubMed  Article  CAS  Google Scholar 

  10. Daigneault M, Preston JA, Marriott HM, Whyte MK, Dockrell DH (2010) The identification of markers of macrophage differentiation in PMA-stimulated THP-1 cells and monocyte-derived macrophages. PLoS One 5:e8668. doi:10.1371/journal.pone.0008668

    PubMed  Article  Google Scholar 

  11. De Meester I, Scharpé S, Vanham G, Bosmans E, Heyligen H, Vanhoof G, Corte G (1993) Antibody binding profile of purified and cell-bound CD26. Designation of BT5/9 and TA5.9 to the CD26 cluster. Immunobiology 188:145–158. doi:10.1016/S0171-2985(11)80494-8

    PubMed  Article  Google Scholar 

  12. De Meyer I, Martinet W, Schrijvers DM, Timmermans JP, Bult H, De Meyer GR (2012) Toll-like receptor 7 stimulation by imiquimod induces macrophage autophagy and inflammation in atherosclerotic plaques. Basic Res Cardiol 107:269. doi:10.1007/s00395-012-0269-1

    PubMed  Article  Google Scholar 

  13. De Meyer I, Martinet W, Van Hove CE, Schrijvers DM, Hoymans VY, Van Vaeck L, Fransen P, Bult H, De Meyer GR (2011) Inhibition of inositol monophosphatase by lithium chloride induces selective macrophage apoptosis in atherosclerotic plaques. Br J Pharmacol 162:1410–1423. doi:10.1111/j.1476-5381.2010.01152.x

    PubMed  Article  Google Scholar 

  14. Deacon CF (2011) Dipeptidyl peptidase-4 inhibitors in the treatment of type 2 diabetes: a comparative review. Diabetes Obes Metab 13:7–18. doi:10.1111/j.1463-1326.2010.01306.x

    PubMed  Article  CAS  Google Scholar 

  15. Dubois V, Van Ginneken C, De Cock H, Lambeir AM, Van der Veken P, Augustyns K, Chen X, Scharpé S, De Meester I (2009) Enzyme activity and immunohistochemical localization of dipeptidyl peptidase 8 and 9 in male reproductive tissues. J Histochem Cytochem 57:531–541. doi:10.1369/jhc.2009.952739

    PubMed  Article  CAS  Google Scholar 

  16. ENCODE (2011) A user’s guide to the encyclopedia of DNA elements. PLoS Biol 9:e1001046. doi:10.1371/journal.pbio.1001046

    Article  Google Scholar 

  17. Friedman AD (2007) Transcriptional control of granulocyte and monocyte development. Oncogene 26:6816–6828. doi:10.1038/sj.onc.1210764

    PubMed  Article  CAS  Google Scholar 

  18. Fukuhara M, Geary RL, Diz DI, Gallagher PE, Wilson JA, Glazier SS, Dean RH, Ferrario CM (2000) Angiotensin-converting enzyme expression in human carotid artery atherosclerosis. Hypertension 35:353–359. doi:10.1161/01.HYP.35.1.353

    PubMed  Article  CAS  Google Scholar 

  19. Fuster V, Badimon L, Badimon JJ, Chesebro JH (1992) The pathogenesis of coronary artery disease and the acute coronary syndromes (1). N Engl J Med 326:242–250. doi:10.1056/NEJM199201233260406

    PubMed  Article  CAS  Google Scholar 

  20. Geiss-Friedlander R, Parmentier N, Moller U, Urlaub H, Van den Eynde BJ, Melchior F (2009) The cytoplasmic peptidase DPP9 is rate-limiting for degradation of proline-containing peptides. J Biol Chem 284:27211–27219. doi:10.1074/jbc.M109.041871

    PubMed  Article  CAS  Google Scholar 

  21. Kohlstedt K, Trouvain C, Namgaladze D, Fleming I (2011) Adipocyte-derived lipids increase angiotensin-converting enzyme (ACE) expression and modulate macrophage phenotype. Basic Res Cardiol 106:205–215. doi:10.1007/s00395-010-0137-9

    PubMed  Article  CAS  Google Scholar 

  22. Krijnen PA, Hahn NE, Kholova I, Baylan U, Sipkens JA, van Alphen FP, Vonk AB, Simsek S, Meischl C, Schalkwijk CG, van Buul JD, van Hinsbergh VW, Niessen HW (2012) Loss of DPP4 activity is related to a prothrombogenic status of endothelial cells: implications for the coronary microvasculature of myocardial infarction patients. Basic Res Cardiol 107:233. doi:10.1007/s00395-011-0233-5

    PubMed  Article  Google Scholar 

  23. Lambeir AM, Durinx C, Scharpé S, De Meester I (2003) Dipeptidyl-peptidase IV from bench to bedside: an update on structural properties, functions, and clinical aspects of the enzyme DPP IV. Crit Rev Clin Lab Sci 40:209–294. doi:10.1080/713609354

    PubMed  Article  CAS  Google Scholar 

  24. Lambeir AM, Scharpé S, De Meester I (2008) DPP4 inhibitors for diabetes—what next? Biochem Pharmacol 76:1637–1643. doi:10.1016/j.bcp.2008.07.029

    PubMed  Article  CAS  Google Scholar 

  25. Lankas GR, Leiting B, Roy RS, Eiermann GJ, Beconi MG, Biftu T, Chan CC, Edmondson S, Feeney WP, He H, Ippolito DE, Kim D, Lyons KA, Ok HO, Patel RA, Petrov AN, Pryor KA, Qian X, Reigle L, Woods A, Wu JK, Zaller D, Zhang X, Zhu L, Weber AE, Thornberry NA (2005) Dipeptidyl peptidase IV inhibition for the treatment of type 2 diabetes: potential importance of selectivity over dipeptidyl peptidases 8 and 9. Diabetes 54:2988–2994. doi:10.2337/diabetes.54.10.2988

    PubMed  Article  CAS  Google Scholar 

  26. Lee HJ, Chen YS, Chou CY, Chien CH, Lin CH, Chang GG, Chen X (2006) Investigation of the dimer interface and substrate specificity of prolyl dipeptidase DPP8. J Biol Chem 281:38653–38662. doi:10.1074/jbc.M603895200

    PubMed  Article  CAS  Google Scholar 

  27. Li L, Najafi AH, Kitlinska JB, Neville R, Laredo J, Epstein SE, Burnett MS, Zukowska Z (2011) Of mice and men: neuropeptide y and its receptors are associated with atherosclerotic lesion burden and vulnerability. J Cardiovasc Transl Res 4:351–362. doi:10.1007/s12265-011-9271-5

    PubMed  Article  Google Scholar 

  28. Lojda Z (1979) Studies on dipeptidyl(amino)peptidase IV (glycyl-proline naphthylamidase). II. Blood vessels. Histochemistry 59:153–166. doi:10.1007/BF00495663

    PubMed  Article  CAS  Google Scholar 

  29. Lu C, Tilan JU, Everhart L, Czarnecka M, Soldin SJ, Mendu DR, Jeha D, Hanafy J, Lee CK, Sun J, Izycka-Swieszewska E, Toretsky JA, Kitlinska J (2011) Dipeptidyl peptidases as survival factors in Ewing sarcoma family of tumors: implications for tumor biology and therapy. J Biol Chem 286:27494–27505. doi:10.1074/jbc.M111.224089

    PubMed  Article  CAS  Google Scholar 

  30. Maes MB, Dubois V, Brandt I, Lambeir AM, Van der Veken P, Augustyns K, Cheng JD, Chen X, Scharpé S, De Meester I (2007) Dipeptidyl peptidase 8/9-like activity in human leukocytes. J Leukoc Biol 81:1252–1257. doi:10.1189/jlb.0906546

    PubMed  Article  CAS  Google Scholar 

  31. Martinet W, Verheye S, De Meyer GR (2007) Selective depletion of macrophages in atherosclerotic plaques via macrophage-specific initiation of cell death. Trends Cardiovasc Med 17:69–75. doi:10.1016/j.tcm.2006.12.004

    PubMed  Article  CAS  Google Scholar 

  32. Matheeussen V, Baerts L, De Meyer G, De Keulenaer G, Van der Veken P, Augustyns K, Dubois V, Scharpe S, De Meester I (2011) Expression and spatial heterogeneity of dipeptidyl peptidases in endothelial cells of conduct vessels and capillaries. Biol Chem 392:189–198. doi:10.1515/BC.2011.002

    PubMed  Article  CAS  Google Scholar 

  33. Matheeussen V, Jungraithmayr W, De Meester I (2012) Dipeptidyl peptidase IV as a therapeutic target in ischemia-reperfusion injury. Pharmacol Ther 136:267–282. doi:10.1016/j.pharmthera.2012.07.012

    PubMed  Article  CAS  Google Scholar 

  34. Matheeussen V, Lambeir AM, Jungraithmayr W, Gomez N, Mc Entee K, Van der Veken P, Scharpe S, De Meester I (2012) Method comparison of dipeptidyl peptidase IV activity assays and their application in biological samples containing reversible inhibitors. Clin Chim Acta 413:456–462. doi:10.1016/j.cca.2011.10.031

    PubMed  Article  CAS  Google Scholar 

  35. Matsubara J, Sugiyama S, Sugamura K, Nakamura T, Fujiwara Y, Akiyama E, Kurokawa H, Nozaki T, Ohba K, Konishi M, Maeda H, Izumiya Y, Kaikita K, Sumida H, Jinnouchi H, Matsui K, Kim-Mitsuyama S, Takeya M, Ogawa H (2012) A dipeptidyl peptidase-4 inhibitor, des-fluoro-sitagliptin, improves endothelial function and reduces atherosclerotic lesion formation in apolipoprotein e-deficient mice. J Am Coll Cardiol 59:265–276. doi:10.1016/j.jacc.2011.07.053

    PubMed  Article  CAS  Google Scholar 

  36. Monami M, Lamanna C, Desideri CM, Mannucci E (2012) DPP-4 inhibitors and lipids: systematic review and meta-analysis. Adv Ther 29:14–25. doi:10.1007/s12325-011-0088-z

    PubMed  Article  CAS  Google Scholar 

  37. Nagashima M, Watanabe T, Terasaki M, Tomoyasu M, Nohtomi K, Kim-Kaneyama J, Miyazaki A, Hirano T (2011) Native incretins prevent the development of atherosclerotic lesions in apolipoprotein E knockout mice. Diabetologia 54:2649–2659. doi:10.1007/s00125-011-2241-2

    PubMed  Article  CAS  Google Scholar 

  38. Olsen C, Wagtmann N (2002) Identification and characterization of human DPP9, a novel homologue of dipeptidyl peptidase IV. Gene 299:185–193. doi:10.1016/S0378-1119(02)01059-4

    PubMed  Article  CAS  Google Scholar 

  39. Pennington KN, Taylor JA, Bren GD, Paya CV (2001) IkappaB kinase-dependent chronic activation of NF-kappaB is necessary for p21(WAF1/Cip1) inhibition of differentiation-induced apoptosis of monocytes. Mol Cell Biol 21:1930–1941. doi:10.1128/MCB.21.6.1930-1941.2001

    PubMed  Article  CAS  Google Scholar 

  40. Pilla E, Moller U, Sauer G, Mattiroli F, Melchior F, Geiss-Friedlander R (2012) A novel SUMO1-specific interacting motif in Dipeptidyl peptidase 9 (DPP9) that is important for enzymatic regulation. J Biol Chem 287:44320–44329. doi:10.1074/jbc.M112.397224

    PubMed  Article  CAS  Google Scholar 

  41. Reinhold D, Goihl A, Wrenger S, Reinhold A, Kuhlmann UC, Faust J, Neubert K, Thielitz A, Brocke S, Tager M, Ansorge S, Bank U (2009) Role of dipeptidyl peptidase IV (DP IV)-like enzymes in T lymphocyte activation: investigations in DP IV/CD26-knockout mice. Clin Chem Lab Med 47:268–274. doi:10.1515/CCLM.2009.062

    PubMed  Article  CAS  Google Scholar 

  42. Ross R (1999) Atherosclerosis—an inflammatory disease. N Engl J Med 340:115–126. doi:10.1056/NEJM199901143400207

    PubMed  Article  CAS  Google Scholar 

  43. Schade J, Stephan M, Schmiedl A, Wagner L, Niestroj AJ, Demuth HU, Frerker N, Klemann C, Raber KA, Pabst R, von Horsten S (2008) Regulation of expression and function of dipeptidyl peptidase 4 (DP4), DP8/9, and DP10 in allergic responses of the lung in rats. J Histochem Cytochem 56:147–155. doi:10.1369/jhc.7A7319.2007

    PubMed  Article  CAS  Google Scholar 

  44. Shah Z, Kampfrath T, Deiuliis JA, Zhong J, Pineda C, Ying Z, Xu X, Lu B, Moffatt-Bruce S, Durairaj R, Sun Q, Mihai G, Maiseyeu A, Rajagopalan S (2011) Long-term dipeptidyl-peptidase 4 inhibition reduces atherosclerosis and inflammation via effects on monocyte recruitment and chemotaxis. Circulation 124:2338–2349. doi:10.1161/CIRCULATIONAHA.111.041418

    PubMed  Article  CAS  Google Scholar 

  45. Skyler JS, Bergenstal R, Bonow RO, Buse J, Deedwania P, Gale EA, Howard BV, Kirkman MS, Kosiborod M, Reaven P, Sherwin RS (2009) Intensive glycemic control and the prevention of cardiovascular events: implications of the ACCORD, ADVANCE, and VA Diabetes Trials: a position statement of the American Diabetes Association and a Scientific Statement of the American College of Cardiology Foundation and the American Heart Association. J Am Coll Cardiol 53:298–304. doi:10.1016/j.jacc.2008.10.008

    PubMed  Article  Google Scholar 

  46. Sordet O, Bettaieb A, Bruey JM, Eymin B, Droin N, Ivarsson M, Garrido C, Solary E (1999) Selective inhibition of apoptosis by TPA-induced differentiation of U937 leukemic cells. Cell Death Differ 6:351–361. doi:10.1038/sj.cdd.4400499

    PubMed  Article  CAS  Google Scholar 

  47. Spagnuolo PA, Hurren R, Gronda M, Maclean N, Datti A, Basheer A, Lin FH, Wang X, Wrana J, Schimmer AD (2013) Inhibition of intracellular dipeptidyl peptidases 8 and 9 enhances parthenolide’s anti-leukemic activity. Leukemia. doi:10.1038/leu.2013.9

  48. Ta NN, Schuyler CA, Li Y, Lopes-Virella MF, Huang Y (2011) DPP-4 (CD26) inhibitor alogliptin inhibits atherosclerosis in diabetic apolipoprotein E-deficient mice. J Cardiovasc Pharmacol 58:157–166. doi:10.1097/FJC.0b013e31821e5626

    PubMed  Article  CAS  Google Scholar 

  49. Tedgui A, Mallat Z (2006) Cytokines in atherosclerosis: pathogenic and regulatory pathways. Physiol Rev 86:515–581. doi:10.1152/physrev.00024.2005

    PubMed  Article  CAS  Google Scholar 

  50. Terasaki M, Nagashima M, Watanabe T, Nohtomi K, Mori Y, Miyazaki A, Hirano T (2012) Effects of PKF275-055, a dipeptidyl peptidase-4 inhibitor, on the development of atherosclerotic lesions in apolipoprotein E-null mice. Metab 61:974–977. doi:10.1016/j.metabol.2011.11.011

    Article  CAS  Google Scholar 

  51. Ussher JR, Drucker DJ (2012) Cardiovascular biology of the incretin system. Endocr Rev 33:187–215. doi:10.1210/er.2011-1052

    PubMed  Article  CAS  Google Scholar 

  52. Valledor AF, Borras FE, Cullell-Young M, Celada A (1998) Transcription factors that regulate monocyte/macrophage differentiation. J Leukoc Biol 63:405–417

    PubMed  CAS  Google Scholar 

  53. Van Goethem S, Matheeussen V, Joossens J, Lambeir AM, Chen X, De Meester I, Haemers A, Augustyns K, Van der Veken P (2011) Structure-activity relationship studies on isoindoline inhibitors of dipeptidyl peptidases 8 and 9 (DPP8, DPP9): is DPP8-selectivity an attainable goal? J Med Chem 54:5737–5746. doi:10.1021/jm200383j

    PubMed  Article  Google Scholar 

  54. Verreck FA, de Boer T, Langenberg DM, van der Zanden L, Ottenhoff TH (2006) Phenotypic and functional profiling of human proinflammatory type-1 and anti-inflammatory type-2 macrophages in response to microbial antigens and IFN-gamma- and CD40L-mediated costimulation. J Leukoc Biol 79:285–293. doi:10.1189/jlb.0105015

    PubMed  Article  CAS  Google Scholar 

  55. Virmani R, Kolodgie FD, Burke AP, Farb A, Schwartz SM (2000) Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol 20:1262–1275. doi:10.1161/01.ATV.20.5.1262

    PubMed  Article  CAS  Google Scholar 

  56. Wu JJ, Tang HK, Yeh TK, Chen CM, Shy HS, Chu YR, Chien CH, Tsai TY, Huang YC, Huang YL, Huang CH, Tseng HY, Jiaang WT, Chao YS, Chen X (2009) Biochemistry, pharmacokinetics, and toxicology of a potent and selective DPP8/9 inhibitor. Biochem Pharmacol 78:203–210. doi:10.1016/j.bcp.2009.03.032

    PubMed  Article  CAS  Google Scholar 

  57. Yan D, Davis FJ, Sharrocks AD, Im HJ (2010) Emerging roles of SUMO modification in arthritis. Gene 466:1–15. doi:10.1016/j.gene.2010.07.003

    PubMed  Article  CAS  Google Scholar 

  58. Ye Y, Perez-Polo JR, Aguilar D, Birnbaum Y (2011) The potential effects of anti-diabetic medications on myocardial ischemia-reperfusion injury. Basic Res Cardiol 106:925–952. doi:10.1007/s00395-011-0216-6

    PubMed  Article  CAS  Google Scholar 

  59. Yu DM, Ajami K, Gall MG, Park J, Lee CS, Evans KA, McLaughlin EA, Pitman MR, Abbott CA, McCaughan GW, Gorrell MD (2009) The in vivo expression of dipeptidyl peptidases 8 and 9. J Histochem Cytochem 57:1025–1040. doi:10.1369/jhc.2009.953760

    PubMed  Article  CAS  Google Scholar 

  60. Yu DM, Yao TW, Chowdhury S, Nadvi NA, Osborne B, Church WB, McCaughan GW, Gorrell MD (2010) The dipeptidyl peptidase IV family in cancer and cell biology. FEBS J 277:1126–1144. doi:10.1111/j.1742-4658.2009.07526.x

    PubMed  Article  CAS  Google Scholar 

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Acknowledgments

This work was supported by the Fund for Scientific Research Flanders (Belgium, FWO-Vlaanderen, Grant no. G016209) and by GOA BOF and TOP BOF (Research Council, Special Fund for Research, University of Antwerp). Veerle Matheeussen and Yannick Waumans are research assistants of FWO-Vlaanderen. We are grateful to Mrs. Rita Van Den Bossche and Mrs. Yani Sim for their excellent technical assistance.

Conflict of interest

The authors declare that they have no conflict of interest.

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Affiliations

  1. Laboratory of Medical Biochemistry, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium

    Veerle Matheeussen, Yannick Waumans, Simon Scharpé & Ingrid De Meester

  2. Laboratory of Physiopharmacology, Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium

    Wim Martinet & Guido R. Y. De Meyer

  3. Laboratory of Medicinal Chemistry, Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium

    Sebastiaan Van Goethem, Pieter Van der Veken & Koen Augustyns

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  1. Veerle Matheeussen
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  2. Yannick Waumans
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  4. Sebastiaan Van Goethem
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Correspondence to Ingrid De Meester.

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Matheeussen, V., Waumans, Y., Martinet, W. et al. Dipeptidyl peptidases in atherosclerosis: expression and role in macrophage differentiation, activation and apoptosis. Basic Res Cardiol 108, 350 (2013). https://doi.org/10.1007/s00395-013-0350-4

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  • DOI: https://doi.org/10.1007/s00395-013-0350-4

Keywords

  • Atherosclerosis
  • DPPIV
  • DPP4
  • DPP8
  • DPP9
  • Macrophage