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Fas Deficiency in Atherosclerosis

DISCOVERIES (ISSN 2359-7232), 2015, January-March issue

CITATION: 

Kubo N, McCurdy S, Boisvert WADefective Fas Expression on Bone Marrow Derived Cells Alters Atherosclerotic Plaque Morphology in Hyperlipidemic Mice. Discoveries 2015, Jan-Mar; 3(1): e37. DOI: 10.15190/d.2015.29

 Submitted: February 12, 2015; RevisedMarch 23, 2015AcceptedMarch 25, 2015Published: March 31, 2015;

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Defective Fas Expression on Bone Marrow Derived Cells Alters Atherosclerotic Plaque Morphology in Hyperlipidemic Mice

Nobuhiko Kubo (1), Sara McCurdy (2), William A. Boisvert (2,*)

(1) Department of Clinical Laboratory Medicine, Omiya Medical Center, Jichi Medical School, Japan; 

(2) Center for Cardiovascular Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, USA

*Correspondence to: William A. Boisvert, PhD, Center for Cardiovascular Research, University of Hawaii John A. Burns School of Medicine, 651 Ilalo Street, Honolulu, HI 96813, USA; Phone: (808) 692-1567; Fax: (808) 692-1973; E-mail: wab@hawaii.edu

Abstract

Fas (CD95) is a member of the TNF-receptor family expressed on a wide range of cells. Interaction of Fas with its receptor, Fas ligand (Fas-L), stimulates an intracellular cascade of events that leads to apoptosis. Because apoptosis of inflammatory cells plays a key role in atherosclerosis we sought to determine the role of Fas in the development of atherosclerosis by repopulating the bone marrow cells of atherosclerosis-prone low density lipoprotein receptor null (LDL-R-/-) mice with either cells from lpr mice (lpr-BMT) that have defective Fas expression or from control mice (WT-BMT). The lpr-BMT mice exhibited no peripheral blood Fas expression 4 weeks after BMT. After consuming an atherogenic diet for 16 weeks, lpr-BMT mice developed atherosclerotic lesions characterized by smaller fibrous area with thinner fibrous cap and less TUNEL-positive staining compared to WT-BMT mice, although overall lesion size in lpr-BMT mice was similar to that of WT-BMT mice. Examination of a series of human atherosclerotic lesions revealed that many Fas-positive cells were colocalized with CD68-positive macrophages. Although apoptotic cells were rarely observed in the foam cell-rich fatty streak lesions, apoptotic CD68-positive macrophages in advanced lesions were detected in areas rich with inflammatory cells near the necrotic core.  These observations suggest that Fas expression by the macrophages in atherosclerotic lesions can influence the plaque morphology towards a more fibrous type

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References

1. Frangogiannis NG. Regulation of the inflammatory response in cardiac repair. Circ Res. 2012; 111(1): 159-73.

View article (DOI)  PubMed

2. Arslan F, de Kleijn DP, Pasterkamp G. Innate immune signaling in cardiac ischemia. Nat Rev Cardiol. 2011; 8(5): 292-300. 

View article (DOI)  PubMed

3. Liehn EA, Postea O, Curaj A, Marx N. Repair after myocardial infarction, between fantasy and reality: the role of chemokines. J Am Coll Cardiol. 2011; 58(23): 2357-62.

View article (DOI)  PubMed

4. Frangogiannis NG. Chemokines in ischemia and reperfusion. Thromb Haemost. 2007; 97(5): 738-47.

View article (DOI)  PubMed

5. Entman ML, Michael L, Rossen RD, Dreyer WJ, Anderson DC, Taylor AA, et al. Inflammation in the course of early myocardial ischemia. Faseb J. 1991; 5(11): 2529-37.

PubMed

6. Roberts R, DeMello V, Sobel BE. Deleterious effects of methylprednisolone in patients with myocardial infarction. Circulation. 1976; 53(3) Suppl: I204-6.

PubMed

7. Christia P, Frangogiannis NG. Targeting inflammatory pathways in myocardial infarction. Eur J Clin Invest. 2013; 43(9): 986-95.

View article (DOI)  PubMed

8. Dinarello CA. A clinical perspective of IL-1beta as the gatekeeper of inflammation. Eur J Immunol. 2011; 41(5): 1203-17.

View article (DOI)  PubMed

9. Dinarello CA. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood. 2011; 117(14): 3720-32.

View article (DOI)  PubMed

10. Masters SL, Simon A, Aksentijevich I, Kastner DL. Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease. Annu Rev Immunol. 2009; 27: 621-68.

View article (DOI)  PubMed 

11. Nam JL, Winthrop KL, van Vollenhoven RF, Pavelka K, Valesini G, Hensor EM, et al. Current evidence for the management of rheumatoid arthritis with biological disease-modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of RA. Ann Rheum Dis. 2010; 69(6): 976-86.

View article (DOI)  PubMed

12. Garlanda C, Dinarello CA, Mantovani A. The interleukin-1 family: back to the future. Immunity. 2013; 39(6): 1003-18.

View article (DOI)  PubMed

13. Netea MG, van de Veerdonk FL, van der Meer JW, Dinarello CA, Joosten LA. Inflammasome-Independent Regulation of IL-1-Family Cytokines. Annu Rev Immunol. 2014, Dec 10. Epub ahead of print.

View article (DOI)  PubMed

14. Agostini L, Martinon F, Burns K, McDermott MF, Hawkins PN, Tschopp J. NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder. Immunity. 2004; 20(3): 319-25.

View article (DOI)  PubMed

15. Colotta F, Re F, Muzio M, Bertini R, Polentarutti N, Sironi M, et al. Interleukin-1 type II receptor: a decoy target for IL-1 that is regulated by IL-4. Science. 1993; 261(5120): 472-5.

View article (DOI)  PubMed

16. Cullinan EB, Kwee L, Nunes P, Shuster DJ, Ju G, McIntyre KW, et al. IL-1 receptor accessory protein is an essential component of the IL-1 receptor. J Immunol. 1998; 161(10): 5614-20.

PubMed

17. Dewald O, Ren G, Duerr GD, Zoerlein M, Klemm C, Gersch C, et al. Of mice and dogs: species-specific differences in the inflammatory response following myocardial infarction. Am J Pathol. 2004; 164(2): 665-77.

View article (DOI)  PubMed

18. Lugrin J, Parapanov R, Rosenblatt-Velin N, Rignault-Clerc S, Feihl F, Waeber B, et al. Cutting Edge: IL-1alpha Is a Crucial Danger Signal Triggering Acute Myocardial Inflammation during Myocardial Infarction. J Immunol. 2015; 194(2): 499-503.

View article (DOI)  PubMed

19. Saxena A, Chen W, Su Y, Rai V, Uche OU, Li N, et al. IL-1 Induces Proinflammatory Leukocyte Infiltration and Regulates Fibroblast Phenotype in the Infarcted Myocardium. J Immunol. 2013; 191(9): 4838-48.

View article (DOI)  PubMed

20. Orn S, Ueland T, Manhenke C, Sandanger O, Godang K, Yndestad A, et al. Increased interleukin-1beta levels are associated with left ventricular hypertrophy and remodelling following acute ST segment elevation myocardial infarction treated by primary percutaneous coronary intervention. J Intern Med. 2012; 272(3): 267-76.

View article (DOI)  PubMed

21. Munkvad S, Gram J, Jespersen J. Interleukin-1 and tumor necrosis factor-alpha in plasma of patients with acute ischemic heart disease who undergo thrombolytic therapy: a randomized, placebo-controlled study. Lymphokine Cytokine Res. 1991; 10(4): 325-7.

PubMed

22. Dinarello CA. Biologic basis for interleukin-1 in disease. Blood. 1996; 87(6): 2095-147.

PubMed

23. Giri JG, Wells J, Dower SK, McCall CE, Guzman RN, Slack J, et al. Elevated levels of shed type II IL-1 receptor in sepsis. Potential role for type II receptor in regulation of IL-1 responses. J Immunol. 1994; 153(12): 5802-9.

PubMed

24. Sandanger O, Ranheim T, Vinge LE, Bliksoen M, Alfsnes K, Finsen AV, et al. The NLRP3 inflammasome is up-regulated in cardiac fibroblasts and mediates myocardial ischaemia-reperfusion injury. Cardiovasc Res. 2013; 99(1): 164-74.

View article (DOI)  PubMed

25. Mezzaroma E, Toldo S, Farkas D, Seropian IM, Van Tassell BW, Salloum FN, et al. The inflammasome promotes adverse cardiac remodeling following acute myocardial infarction in the mouse. Proc Natl Acad Sci U S A. 2011; 108(49): 19725-30.

View article (DOI)  PubMed

26. Kawaguchi M, Takahashi M, Hata T, Kashima Y, Usui F, Morimoto H, et al. Inflammasome activation of cardiac fibroblasts is essential for myocardial ischemia/reperfusion injury. Circulation. 2011; 123(6): 594-604.

View article (DOI)  PubMed

27. Woldbaek PR, Tonnessen T, Henriksen UL, Florholmen G, Lunde PK, Lyberg T, et al. Increased cardiac IL-18 mRNA, pro-IL-18 and plasma IL-18 after myocardial infarction in the mouse; a potential role in cardiac dysfunction. Cardiovasc Res. 2003; 59(1): 122-31.

View article (DOI)  PubMed

28. Toldo S, Mezzaroma E, O'Brien L, Marchetti C, Seropian IM, Voelkel NF, et al. Interleukin-18 mediates interleukin-1-induced cardiac dysfunction. Am J Physiol Heart Circ Physiol. 2014; 306(7): H1025-31.

View article (DOI)  PubMed

29. Mallat Z, Henry P, Fressonnet R, Alouani S, Scoazec A, Beaufils P, et al. Increased plasma concentrations of interleukin-18 in acute coronary syndromes. Heart. 2002; 88 5: 467-9.

View article (DOI)  PubMed

30. 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(6): 1538-49.

View article (DOI)  PubMed

31. Seki K, Sanada S, Kudinova AY, Steinhauser ML, Handa V, Gannon J, et al. Interleukin-33 prevents apoptosis and improves survival after experimental myocardial infarction through ST2 signaling. Circ Heart Fail. 2009; 2(6): 684-91.

View article (DOI)  PubMed

32. Sabatine MS, Morrow DA, Higgins LJ, MacGillivray C, Guo W, Bode C, et al. Complementary roles for biomarkers of biomechanical strain ST2 and N-terminal prohormone B-type natriuretic peptide in patients with ST-elevation myocardial infarction. Circulation. 2008; 117(15): 1936-44.

View article (DOI)  PubMed

33. Bonetti A, Marchini M, Ortolani F. Immunolocalization of interleukin-1 receptor antagonist in healthy and infarcted myocardium. Histol Histopathol. 2008; 23(9): 1093-102.

PubMed

34. Latini R, Bianchi M, Correale E, Dinarello CA, Fantuzzi G, Fresco C, et al. Cytokines in acute myocardial infarction: selective increase in circulating tumor necrosis factor, its soluble receptor, and interleukin-1 receptor antagonist. J Cardiovasc Pharmacol. 1994; 23(1): 1-6.

PubMed

35. Patti G, D'Ambrosio A, Mega S, Giorgi G, Zardi EM, Zardi DM, et al. Early interleukin-1 receptor antagonist elevation in patients with acute myocardial infarction. J Am Coll Cardiol. 2004; 43(1): 35-8.

View article (DOI)  PubMed

36. Patti G, Mega S, Pasceri V, Nusca A, Giorgi G, Zardi EM, et al. Interleukin-1 receptor antagonist levels correlate with extent of myocardial loss in patients with acute myocardial infarction. Clin Cardiol. 2005; 28(4): 193-6.

PubMed

37. Shibata M, Endo S, Inada K, Kuriki S, Harada M, Takino T, et al. Elevated plasma levels of interleukin-1 receptor antagonist and interleukin-10 in patients with acute myocardial infarction. J Interferon Cytokine Res. 1997; 17(3): 145-50.

PubMed

38. Bujak M, Frangogiannis NG. The role of IL-1 in the pathogenesis of heart disease. Arch Immunol Ther Exp (Warsz). 2009; 57(3): 165-76.

View article (DOI)  PubMed

39. Frangogiannis NG. The immune system and the remodeling infarcted heart: cell biological insights and therapeutic opportunities. J Cardiovasc Pharmacol. 2014; 63(3): 185-95.

View article (DOI)  PubMed

40. O'Brien LC, Mezzaroma E, Van Tassell BW, Marchetti C, Carbone S, Abbate A, et al. Interleukin-18 as a therapeutic target in acute myocardial infarction and heart failure. Mol Med. 2014; 20: 221-9.

View article (DOI)  PubMed

41. Ing DJ, Zang J, Dzau VJ, Webster KA, Bishopric NH. Modulation of cytokine-induced cardiac myocyte apoptosis by nitric oxide, Bak, and Bcl-x. Circ Res. 1999; 84(1): 21-33.

View article (DOI)  PubMed

42. Suzuki K, Murtuza B, Smolenski RT, Sammut IA, Suzuki N, Kaneda Y, et al. Overexpression of interleukin-1 receptor antagonist provides cardioprotection against ischemia-reperfusion injury associated with reduction in apoptosis. Circulation. 2001; 104(12) Suppl 1: I308-I3.

View article (DOI)  PubMed

43. Abbate A, Salloum FN, Vecile E, Das A, Hoke NN, Straino S, et al. Anakinra, a recombinant human interleukin-1 receptor antagonist, inhibits apoptosis in experimental acute myocardial infarction. Circulation. 2008; 117(20): 2670-83.

View article (DOI)  PubMed

44. Bujak M, Dobaczewski M, Chatila K, Mendoza LH, Li N, Reddy A, et al. Interleukin-1 receptor type I signaling critically regulates infarct healing and cardiac remodeling. Am J Pathol. 2008; 173(1): 57-67.

View article (DOI)  PubMed

45. Colotta F, Borre A, Wang JM, Tattanelli M, Maddalena F, Polentarutti N, et al. Expression of a monocyte chemotactic cytokine by human mononuclear phagocytes. J Immunol. 1992; 148(3): 760-5.

PubMed

46. Colotta F, Re F, Polentarutti N, Sozzani S, Mantovani A. Modulation of granulocyte survival and programmed cell death by cytokines and bacterial products. Blood. 1992; 80(8): 2012-20.

PubMed

47. Shinde AV, Frangogiannis NG. Fibroblasts in myocardial infarction: A role in inflammation and repair. J Mol Cell Cardiol. 2014; 70C: 74-82.

View article (DOI)  PubMed

48. Turner NA, Das A, Warburton P, O'Regan DJ, Ball SG, Porter KE. Interleukin-1alpha stimulates proinflammatory cytokine expression in human cardiac myofibroblasts. Am J Physiol Heart Circ Physiol. 2009; 297(3): H1117-27.

View article (DOI)  PubMed

49. Turner NA, Warburton P, O'Regan DJ, Ball SG, Porter KE. Modulatory effect of interleukin-1alpha on expression of structural matrix proteins, MMPs and TIMPs in human cardiac myofibroblasts: role of p38 MAP kinase. Matrix Biol. 2010; 29(7): 613-20.

View article (DOI)  PubMed

50. Siwik DA, Chang DL, Colucci WS. Interleukin-1beta and tumor necrosis factor-alpha decrease collagen synthesis and increase matrix metalloproteinase activity in cardiac fibroblasts in vitro. Circ Res. 2000; 86(12): 1259-65.

View article (DOI)  PubMed

51. Murtuza B, Suzuki K, Bou-Gharios G, Beauchamp JR, Smolenski RT, Partridge TA, et al. Transplantation of skeletal myoblasts secreting an IL-1 inhibitor modulates adverse remodeling in infarcted murine myocardium. Proc Natl Acad Sci U S A. 2004; 101(12): 4216-21.

View article (DOI)  PubMed

52. Berk BC, Fujiwara K, Lehoux S. ECM remodeling in hypertensive heart disease. J Clin Invest. 2007; 117(3): 568-75.

PubMed

53. Kong P, Christia P, Frangogiannis NG. The pathogenesis of cardiac fibrosis. Cell Mol Life Sci. 2014; 71(4): 549-74.

View article (DOI)  PubMed

54. Frangogiannis NG, Mendoza LH, Lindsey ML, Ballantyne CM, Michael LH, Smith CW, et al. IL-10 is induced in the reperfused myocardium and may modulate the reaction to injury. J Immunol. 2000; 165(5): 2798-808.

View article (DOI)  PubMed

55. Dobaczewski M, Chen W, Frangogiannis NG. Transforming growth factor (TGF)-beta signaling in cardiac remodeling. J Mol Cell Cardiol. 2011; 51(4): 600-6.

View article (DOI)  PubMed

56. Zymek P, Nah DY, Bujak M, Ren G, Koerting A, Leucker T, et al. Interleukin-10 is not a critical regulator of infarct healing and left ventricular remodeling. Cardiovasc Res. 2007; 74(2): 313-22.

View article (DOI)  PubMed

57. Deroide N, Li X, Lerouet D, Van Vre E, Baker L, Harrison J, et al. MFGE8 inhibits inflammasome-induced IL-1beta production and limits postischemic cerebral injury. J Clin Invest. 2013; 123(3): 1176-81.

View article (DOI)  PubMed

58. Chen W, Saxena A, Li N, Sun J, Gupta A, Lee DW, et al. Endogenous IRAK-M attenuates postinfarction remodeling through effects on macrophages and fibroblasts. Arterioscler Thromb Vasc Biol. 2012; 32(11): 2598-608.

View article (DOI)  PubMed

59. Nahrendorf M, Swirski FK, Aikawa E, Stangenberg L, Wurdinger T, Figueiredo JL, et al. The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J Exp Med. 2007; 204(12): 3037-47.

PubMed

60. Weirather J, Hofmann UD, Beyersdorf N, Ramos GC, Vogel B, Frey A, et al. Foxp3+ CD4+ T cells improve healing after myocardial infarction by modulating monocyte/macrophage differentiation. Circ Res. 2014; 115(1): 55-67.

View article (DOI)  PubMed

61. Saxena A, Dobaczewski M, Rai V, Haque Z, Chen W, Li N, et al. Regulatory T cells are recruited in the infarcted mouse myocardium and may modulate fibroblast phenotype and function. Am J Physiol Heart Circ Physiol. 2014; 307(8):H1233-42.

View article (DOI)  PubMed

62. Mann DL. Targeted anticytokine therapy and the failing heart. Am J Cardiol. 2005; 95(11A): 9C-16C; discussion 38C-40C.

View article (DOI)  PubMed

63. Burchfield JS, Dong JW, Sakata Y, Gao F, Tzeng HP, Topkara VK, et al. The cytoprotective effects of tumor necrosis factor are conveyed through tumor necrosis factor receptor-associated factor 2 in the heart. Circ Heart Fail. 2010; 3(1): 157-64.

View article (DOI)  PubMed

64. Haudek SB, Taffet GE, Schneider MD, Mann DL. TNF provokes cardiomyocyte apoptosis and cardiac remodeling through activation of multiple cell death pathways. J Clin Invest. 2007; 117(9): 2692-701.

View article (DOI)  PubMed

65. Hwang MW, Matsumori A, Furukawa Y, Ono K, Okada M, Iwasaki A, et al. Neutralization of interleukin-1beta in the acute phase of myocardial infarction promotes the progression of left ventricular remodeling. J Am Coll Cardiol. 2001; 38(5): 1546-53.

View article (DOI)  PubMed

66. Ridker PM, Thuren T, Zalewski A, Libby P. Interleukin-1beta inhibition and the prevention of recurrent cardiovascular events: rationale and design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS). Am Heart J. 2011; 162(4): 597-605.

View article (DOI)  PubMed

67. Abbate A, Kontos MC, Grizzard JD, Biondi-Zoccai GG, Van Tassell BW, Robati R, et al. Interleukin-1 blockade with anakinra to prevent adverse cardiac remodeling after acute myocardial infarction (Virginia Commonwealth University Anakinra Remodeling Trial [VCU-ART] Pilot study). Am J Cardiol. 2010; 105(10): 1371-7 e1.

View article (DOI)  PubMed

68. Abbate A, Van Tassell BW, Biondi-Zoccai G, Kontos MC, Grizzard JD, Spillman DW, et al. Effects of interleukin-1 blockade with anakinra on adverse cardiac remodeling and heart failure after acute myocardial infarction [from the Virginia Commonwealth University-Anakinra Remodeling Trial (2) (VCU-ART2) pilot study]. Am J Cardiol. 2013; 111(10): 1394-400.

View article (DOI)  PubMed

69. Abbate A, Kontos MC, Abouzaki NA, Melchior RD, Thomas C, Van Tassell BW, et al. Comparative safety of interleukin-1 blockade with anakinra in patients with ST-segment elevation acute myocardial infarction (from the VCU-ART and VCU-ART2 pilot studies). Am J Cardiol. 2015; 115(3): 288-92.

View article (DOI)  PubMed

70. Frangogiannis NG. The prognostic value of monocyte chemoattractant protein-1/CCL2 in acute coronary syndromes. J Am Coll Cardiol. 2007; 50(22): 2125-7.

View article (DOI)  PubMed

71. Frangogiannis NG. Biomarkers: hopes and challenges in the path from discovery to clinical practice. Transl Res. 2012; 159(4): 197-204.

View article (DOI)  PubMed

72. Venkatachalam K, Prabhu SD, Reddy VS, Boylston WH, Valente AJ, Chandrasekar B. Neutralization of interleukin-18 ameliorates ischemia/reperfusion-induced myocardial injury. J Biol Chem. 2009; 284(12): 7853-65.

View article (DOI)  PubMed

73. Wang M, Tan J, Wang Y, Meldrum KK, Dinarello CA, Meldrum DR. IL-18 binding protein-expressing mesenchymal stem cells improve myocardial protection after ischemia or infarction. Proc Natl Acad Sci U S A. 2009; 106(41): 17499-504.

View article (DOI)  PubMed

 

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