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Heart Failure Reviews

, Volume 21, Issue 5, pp 489–497 | Cite as

Targeting BNIP3 in inflammation-mediated heart failure: a novel concept in heart failure therapy

  • Patrick Asare Fordjour
  • Lingyang Wang
  • Hui Gao
  • Lan Li
  • Yadong Wang
  • Makafui Nyagblordzro
  • Kojo Agyemang
  • Guanwei Fan
Article

Abstract

Myocardial injury activates inflammatory mediators and provokes the integration of BCL-2/adenovirus E1B 19KD interacting protein 3 (BNIP3) into mitochondrial membranes. Translocation of BNIP3 to mitochondria inexorably causes mitochondrial fragmentation. Heart failure (HF) epitomizes the life-threatening phase of BNIP3-induced mitochondrial dysfunction and cardiomyocyte death. Available data suggest that inflammatory mediators play a key role in cardiac cell demise and have been implicated in the pathogenesis of HF syndrome. In the present study, we reviewed the changes in BNIP3 protein expression levels during inflammatory response and postulated its role in inflammation-mediated HF. We also identified inflammatory mediators’ response such as stimulation of TNF-α and NO as potent inducer of BNIP3. Previous studies suggest that the pro-apoptotic protein has a common regulator with IL-1β and induces IL-6-stimulated cardiac hypertrophy. These findings corroborate our contention that interventions designed to functionally modulate BNIP3 activity during inflammatory-mediated HF may prove beneficial in preventing HF. Such a revelation will open new avenue for further research to unravel a novel therapeutic strategy in HF diseases. Moreover, understanding of the relationship between BNIP3 and inflammatory mediators in HF pathologies will not only contribute to the discovery of drugs that can inhibit inflammation-mediated heart diseases, but also enhance the current knowledge on the key role BNIP3 plays during inflammation.

Keywords

BNIP3 Heart failure Inflammation Endoplasmic reticulum calcium 

Notes

Acknowledgments

This work was supported by Grant from the National Key Basic Research Program of China (973 Program) (No. 2012CB518404), the National Natural Science Foundation of China (81273891), the National Science and Technology Support Program Projects (2014BAI05B01), and the Program for Changjiang Scholars and Innovative Research Team in University (IRT1276).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Human and animals rights

This article does not contain any studies with human participants or animals performed by any of the authors.

References

  1. 1.
    Ramani GV, Uber PA, Mehra MR (2010) Chronic heart failure: contemporary diagnosis and management. Mayo Clin Proc 85(2):180–195CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Kuzmicic J, Del Campo A, Lopez-Crisosto C, Morales PE, Pennanen C, Bravo-Sagua R et al (2011) Mitochondrial dynamics: a potential new therapeutic target for heart failure. Rev Esp Cardiol 64(10):916–923CrossRefPubMedGoogle Scholar
  3. 3.
    Parra V, Verdejo H, del Campo A, Pennanen C, Kuzmicic J, Iglewski M et al (2011) The complex interplay between mitochondrial dynamics and cardiac metabolism. J Bioenerg Biomembr 43(1):47–51CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Willerson JT, Ridker PM (2004) Inflammation as a cardiovascular risk factor. Circulation 109(21 suppl 1):II-2–II-10Google Scholar
  5. 5.
    Libby P (2006) Inflammation and cardiovascular disease mechanisms. Clin Nutr 83(2):456–460Google Scholar
  6. 6.
    Anker SD, von Haehling S (2004) Inflammatory mediators in chronic heart failure: an overview. Heart 90(4):464–470CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Oikonomou E, Tousoulis D, Siasos G, Zaromitidou M, Papavassiliou AG, Stefanadis C (2011) The role of inflammation in heart failure: new therapeutic approaches. Hellenic J Cardiol 52(1):30–40 Epub 2011/02/05 PubMedGoogle Scholar
  8. 8.
    Charakida M, Halcox JPJ (2005) Tumor necrosis factor-alpha in heart failure: more questions than answers. Rev Esp Cardiol (English Version) 58(05):470–472CrossRefGoogle Scholar
  9. 9.
    Yndestad A, Damas JK, Oie E, Ueland T, Gullestad L, Aukrust P (2006) Systemic inflammation in heart failure–the whys and wherefores. Heart Fail Rev 11(1):83–92 Epub 2006/07/05 CrossRefPubMedGoogle Scholar
  10. 10.
    Kim JY, Kim YJ, Lee S, Park JH (2011) BNip3 is a mediator of TNF-induced necrotic cell death. Apoptosis 16(2):114–126 Epub 2010/10/22 CrossRefPubMedGoogle Scholar
  11. 11.
    Ghavami S, Eshraghi M, Kadkhoda K, Mutawe MM, Maddika S, Bay GH et al (2009) Role of BNIP3 in TNF-induced cell death—TNF upregulates BNIP3 expression. Biochim Biophys Acta (BBA) Mol Cell Res 1793(3):546–560CrossRefGoogle Scholar
  12. 12.
    Ghavami S, Eshraghi M, Kadkhoda K, Mutawe MM, Maddika S, Bay GH et al (2009) Role of BNIP3 in TNF-induced cell death–TNF upregulates BNIP3 expression. Biochim Biophys Acta 1793(3):546–560 Epub 2009/03/27 CrossRefPubMedGoogle Scholar
  13. 13.
    Yook YH, Kang KH, Maeng O, Kim TR, Lee JO, Kang KI et al (2004) Nitric oxide induces BNIP3 expression that causes cell death in macrophages. Biochem Biophys Res Commun 321(2):298–305 Epub 2004/09/11 CrossRefPubMedGoogle Scholar
  14. 14.
    Diwan A, Krenz M, Syed FM, Wansapura J, Ren X, Koesters AG et al (2007) Inhibition of ischemic cardiomyocyte apoptosis through targeted ablation of Bnip3 restrains postinfarction remodeling in mice. J Clin Investig 117(10):2825–2833CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Zhang J, Ney PA (2009) Role of BNIP3 and NIX in cell death, autophagy, and mitophagy. Cell Death Differ 16(7):939–946CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Burton TR, Gibson SB (2009) The role of Bcl-2 family member BNIP3 in cell death and disease: NIPping at the heels of cell death. Cell Death Differ 16(4):515–523CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Narula J, Haider N, Virmani R, DiSalvo TG, Kolodgie FD, Hajjar RJ et al (1996) Apoptosis in myocytes in end-stage heart failure. N Engl J Med 335(16):1182–1189CrossRefPubMedGoogle Scholar
  18. 18.
    Narula J, Kolodgie FD, Virmani R (2000) Apoptosis and cardiomyopathy. Curr Opin Cardiol 15(3):183–188CrossRefPubMedGoogle Scholar
  19. 19.
    Hamacher-Brady A, Brady NR, Gottlieb RA, Gustafsson AB (2006) Autophagy as a protective response to Bnip3-mediated apoptotic signaling in the heart. Autophagy 2(4):307–309CrossRefPubMedGoogle Scholar
  20. 20.
    Galvez AS, Brunskill EW, Marreez Y, Benner BJ, Regula KM, Kirschenbaum LA et al (2006) Distinct pathways regulate proapoptotic Nix and BNip3 in cardiac stress. J Biol Chem 281(3):1442–1448CrossRefPubMedGoogle Scholar
  21. 21.
    Chaanine AH, Gordon RE, Kohlbrenner E, Benard L, Jeong D, Hajjar RJ (2013) Potential role of BNIP3 in cardiac remodeling, myocardial stiffness, and endoplasmic reticulum: mitochondrial calcium homeostasis in diastolic and systolic heart failure. Circ Heart Fail 6(3):572–583CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Lee Y, Kubli DA, Hanna RA, Cortez MQ, Lee HY, Miyamoto S et al (2015) Cellular redox status determines sensitivity to BNIP3-mediated cell death in cardiac myocytes. Am J Physiol Cell Physiol 25:00273Google Scholar
  23. 23.
    Graham RM, Frazier DP, Thompson JW, Haliko S, Li H, Wasserlauf BJ et al (2004) A unique pathway of cardiac myocyte death caused by hypoxia–acidosis. J Exp Biol 207(18):3189–3200CrossRefPubMedGoogle Scholar
  24. 24.
    Chinnadurai G, Vijayalingam S, Gibson SB (2009) BNIP3 subfamily BH3-only proteins: mitochondrial stress sensors in normal and pathological functions. Oncogene 27(S1):S114–S127Google Scholar
  25. 25.
    Zhang L, Li L, Liu H, Borowitz JL, Isom GE (2009) BNIP3 mediates cell death by different pathways following localization to endoplasmic reticulum and mitochondrion. FASEB J 23(10):3405–3414CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Regula KM, Ens K, Kirshenbaum LA (2002) Inducible expression of BNIP3 provokes mitochondrial defects and hypoxia-mediated cell death of ventricular myocytes. Circ Res 91(3):226–231CrossRefPubMedGoogle Scholar
  27. 27.
    Gustafsson AB (2011) Bnip3 as a dual regulator of mitochondrial turnover and cell death in the myocardium. Pediatr Cardiol 32(3):267–274CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Hamacher-Brady A, Brady NR, Logue SE, Sayen MR, Jinno M, Kirshenbaum LA et al (2006) Response to myocardial ischemia//reperfusion injury involves Bnip3 and autophagy. Cell Death Differ 14(1):146–157CrossRefPubMedGoogle Scholar
  29. 29.
    Dorn GW 2nd (2010) Mitochondrial pruning by Nix and BNip3: an essential function for cardiac-expressed death factors. J Cardiovasc Transl Res 3(4):374–383CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Vasagiri N, Kutala VK (2014) Structure, function, and epigenetic regulation of BNIP3: a pathophysiological relevance. Mol Biol Rep 41(11):7705–7714CrossRefPubMedGoogle Scholar
  31. 31.
    Levine B, Mizushima N, Virgin HW (2011) Autophagy in immunity and inflammation. Nature 469(7330):323–335CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Djavaheri-Mergny M, Amelotti M, Mathieu J, Besancon F, Bauvy C, Souquere S et al (2006) NF-κB activation represses tumor necrosis factor-alpha-induced autophagy. J Biol Chem 281(41):30373–30382 Epub 2006/07/22 CrossRefPubMedGoogle Scholar
  33. 33.
    Kaltschmidt B, Kaltschmidt C, Hofmann TG, Hehner SP, Droge W, Schmitz ML (2000) The pro- or anti-apoptotic function of NF-κB is determined by the nature of the apoptotic stimulus. Eur J Biochem/FEBS 267(12):3828–3835 Epub 2000/06/10 CrossRefGoogle Scholar
  34. 34.
    Rosca MG, Hoppel CL (2013) Mitochondrial dysfunction in heart failure. Heart Fail Rev. doi: 10.1007/s10741-012-9340-0 PubMedPubMedCentralGoogle Scholar
  35. 35.
    Montaigne D, Hurt C, Neviere R (2012) Mitochondria death/survival signaling pathways in cardiotoxicity induced by anthracyclines and anticancer-targeted therapies. Biochem Res Int 2012:951539CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Wang C, Youle RJ (2009) The role of mitochondria in apoptosis*. Annu Rev Genet 43:95–118CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Chiong M, Wang ZV, Pedrozo Z, Cao DJ, Troncoso R, Ibacache M et al (2011) Cardiomyocyte death: mechanisms and translational implications. Cell Death Dis 22(2):130Google Scholar
  38. 38.
    Prabhakaran K, Li L, Zhang L, Borowitz JL, Isom GE (2007) Upregulation of BNIP3 and translocation to mitochondria mediates cyanide-induced apoptosis in cortical cells. Neuroscience 150(1):159–167CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Chen L, Knowlton AA (2011) Mitochondrial dynamics in heart failure. Congest Heart Fail (Greenwich, Conn) 17(6):257–261CrossRefGoogle Scholar
  40. 40.
    Shires SE, Gustafsson AB (2015) Mitophagy and heart failure. J Mol Med 93(3):253–262CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Crow MT (2002) Hypoxia, BNip3 proteins, and the mitochondrial death pathway in cardiomyocytes. Circ Res 91(3):183–185CrossRefPubMedGoogle Scholar
  42. 42.
    Syed F, Odley A, Hahn HS, Brunskill EW, Lynch RA, Marreez Y et al (2004) Physiological growth synergizes with pathological genes in experimental cardiomyopathy. Circ Res 95(12):1200–1206CrossRefPubMedGoogle Scholar
  43. 43.
    Fordjour PA, Wang Y, Shi Y, Agyemang K, Akinyi M, Zhang Q et al (2015) Possible mechanisms of C-reactive protein mediated acute myocardial infarction. Eur J Pharmacol 760:72–80 Epub 2015/04/22 CrossRefPubMedGoogle Scholar
  44. 44.
    Muller-Werdan U, Buerke M, Ebelt H, Heinroth KM, Herklotz A, Loppnow H et al (2006) Septic cardiomyopathy—a not yet discovered cardiomyopathy? Exp Clin Cardiol 11(3):226–236PubMedPubMedCentralGoogle Scholar
  45. 45.
    Lisman KA, Stetson SJ, Koerner MM, Farmer JA, Torre-Amione G (2002) The role of tumor necrosis factor alpha blockade in the treatment of congestive heart failure. Congest Heart Fail (Greenwich, Conn) 8(5):275–279 Epub 2002/10/09 CrossRefGoogle Scholar
  46. 46.
    Cicoira M, Anker SD, Ronco C (2011) Cardio-renal cachexia syndromes (CRCS): pathophysiological foundations of a vicious pathological circle. J Cachexia Sarcopenia Muscle 2(3):135–142CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Raymond RJ, Dehmer GJ, Theoharides TC, Deliargyris EN (2001) Elevated interleukin-6 levels in patients with asymptomatic left ventricular systolic dysfunction. Am Heart J 141(3):435–438 Epub 2001/03/07 CrossRefPubMedGoogle Scholar
  48. 48.
    Parissis JT, Nikolaou M, Farmakis D, Paraskevaidis IA, Bistola V, Venetsanou K et al (2009) Self-assessment of health status is associated with inflammatory activation and predicts long-term outcomes in chronic heart failure. Eur J Heart Fail 11(2):163–169 Epub 2009/01/27 CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Pepys MB, Hirschfield GM, Tennent GA, Ruth Gallimore J, Kahan MC, Bellotti V et al (2006) Targeting C-reactive protein for the treatment of cardiovascular disease. Nature 440(7088):1217–1221CrossRefPubMedGoogle Scholar
  50. 50.
    Fearon WF, Fearon DT (2008) Inflammation and cardiovascular disease: role of the interleukin-1 receptor antagonist. Circulation 117(20):2577–2579CrossRefPubMedGoogle Scholar
  51. 51.
    Zhang S, Zhang Z, Sandhu G, Ma X, Yang X, Geiger JD et al (2007) Evidence of oxidative stress-induced BNIP3 expression in amyloid beta neurotoxicity. Brain Res 1138:221–230CrossRefPubMedGoogle Scholar
  52. 52.
    Quinsay MN, Thomas RL, Lee Y, Gustafsson AB (2010) Bnip3-mediated mitochondrial autophagy is independent of the mitochondrial permeability transition pore. Autophagy 6(7):855–862CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Rikka S, Quinsay MN, Thomas RL, Kubli DA, Zhang X, Murphy AN et al (2011) Bnip3 impairs mitochondrial bioenergetics and stimulates mitochondrial turnover. Cell Death Differ 18(4):721–731CrossRefPubMedGoogle Scholar
  54. 54.
    Morin D, Assaly R, Paradis S, Berdeaux A (2009) Inhibition of mitochondrial membrane permeability as a putative pharmacological target for cardioprotection. Curr Med Chem 16(33):4382–4398CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Prabhakaran K, Chapman GD, Gunasekar PG (2009) BNIP3 up-regulation and mitochondrial dysfunction in manganese-induced neurotoxicity. Neurotoxicology 30(3):414–422CrossRefPubMedGoogle Scholar
  56. 56.
    Lawrence T (2009) The nuclear factor NF-κB pathway in inflammation. Cold Spring Harb Perspect Biol 1(6):a001651CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Trocoli A, Djavaheri-Mergny M (2011) The complex interplay between autophagy and NF-κB signaling pathways in cancer cells. Am J Cancer Res 1(5):629–649PubMedGoogle Scholar
  58. 58.
    Dorn GW (2009) Apoptotic and non-apoptotic programmed cardiomyocyte death in ventricular remodelling. Cardiovasc Res 81(3):465–473CrossRefPubMedGoogle Scholar
  59. 59.
    Diwan A, Dorn GW (2007) Decompensation of cardiac hypertrophy: cellular mechanisms and novel therapeutic targets. Physiology (Bethesda) 22:56–64CrossRefGoogle Scholar
  60. 60.
    Weng YJ, Kuo WW, Kuo CH, Tung KC, Tsai CH, Lin JA et al (2010) BNIP3 induces IL6 and calcineurin/NFAT3 hypertrophic-related pathways in H9c2 cardiomyoblast cells. Mol Cell Biochem 345(1–2):241–247 Epub 2010/09/21 CrossRefPubMedGoogle Scholar
  61. 61.
    Krenek P, Kmecova J, Kucerova D, Bajuszova Z, Musil P, Gazova A et al (2009) Isoproterenol-induced heart failure in the rat is associated with nitric oxide-dependent functional alterations of cardiac function. Eur J Heart Fail 11(2):140–146 Epub 2009/01/27 CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Beg AA, Baltimore D (1996) An essential role for NF-κB in preventing TNF-α-induced cell death. Science 274(5288):782–784CrossRefPubMedGoogle Scholar
  63. 63.
    Yurkova N, Shaw J, Blackie K, Weidman D, Jayas R, Flynn B et al (2008) The cell cycle factor E2F-1 activates Bnip3 and the intrinsic death pathway in ventricular myocytes. Circ Res 102(4):472–479CrossRefPubMedGoogle Scholar
  64. 64.
    Gang H, Dhingra R, Wang Y, Mughal W, Gordon JW, Kirshenbaum LA (2011) Epigenetic regulation of E2F-1-dependent Bnip3 transcription and cell death by nuclear factor-κB and histone deacetylase-1. Pediatr Cardiol 32(3):263–266CrossRefPubMedGoogle Scholar
  65. 65.
    Baetz D, Regula KM, Ens K, Shaw J, Kothari S, Yurkova N et al (2005) Nuclear factor-κB–mediated cell survival involves transcriptional silencing of the mitochondrial death gene BNIP3 in ventricular myocytes. Circulation 112(24):3777–3785CrossRefPubMedGoogle Scholar
  66. 66.
    Shaw J, Zhang T, Rzeszutek M, Yurkova N, Baetz D, Davie JR et al (2006) Transcriptional silencing of the death gene BNIP3 by cooperative action of NF-κB and histone deacetylase 1 in ventricular myocytes. Circ Res 99(12):1347–1354CrossRefPubMedGoogle Scholar
  67. 67.
    Gordon JW, Shaw JA, Kirshenbaum LA (2011) Multiple facets of NF-κB in the heart: to be or not to NF-κB. Circ Res 108(9):1122–1132CrossRefPubMedGoogle Scholar
  68. 68.
    Lakshmi SV, Naushad SM, Reddy CA, Saumya K, Rao DS, Kotamraju S et al (2013) Oxidative stress in coronary artery disease: epigenetic perspective. Mol Cell Biochem 374(1–2):203–211CrossRefPubMedGoogle Scholar
  69. 69.
    Murai M, Toyota M, Satoh A, Suzuki H, Akino K, Mita H et al (2005) Aberrant DNA methylation associated with silencing BNIP3 gene expression in haematopoietic tumours. Br J Cancer 92(6):1165–1172CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Okami J, Simeone DM, Logsdon CD (2004) Silencing of the hypoxia-inducible cell death protein BNIP3 in pancreatic cancer. Cancer Res 64(15):5338–5346CrossRefPubMedGoogle Scholar
  71. 71.
    Gheorghiade M, Sopko G, De Luca L, Velazquez EJ, Parker JD, Binkley PF et al (2006) Navigating the crossroads of coronary artery disease and heart failure. Circulation 114(11):1202–1213CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Patrick Asare Fordjour
    • 1
    • 2
    • 3
  • Lingyang Wang
    • 1
    • 2
    • 3
  • Hui Gao
    • 1
    • 2
    • 3
  • Lan Li
    • 1
    • 2
    • 3
  • Yadong Wang
    • 1
    • 2
    • 3
  • Makafui Nyagblordzro
    • 1
    • 2
    • 3
  • Kojo Agyemang
    • 1
    • 2
    • 3
  • Guanwei Fan
    • 1
    • 2
    • 3
  1. 1.State Key Laboratory of Modern Chinese MedicineTianjin University of Traditional Chinese MedicineTianjinChina
  2. 2.Ministry of Education Key Laboratory of Pharmacology of Traditional Chinese Medical FormulaeTianjin University of Traditional Chinese MedicineTianjinChina
  3. 3.Institute of Traditional Chinese Medicine ResearchTianjin University of Traditional Chinese MedicineTianjinChina

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