Skip to main content

Advertisement

SpringerLink
Log in

Soluble TNF-related apoptosis induced ligand (sTRAIL) is augmented by Post-Conditioning and correlates to infarct size and left ventricle dysfunction in STEMI patients: a substudy from a randomized clinical trial

  • Original Article
  • Published:
Heart and Vessels Aims and scope Submit manuscript

Abstract

Low levels of Soluble TNF-related apoptosis induced ligand (sTRAIL) seem to be related to worse prognosis after an acute coronary syndrome. PostConditioning (PostCond) may protect the heart from reperfusion injury. We sought to evaluate the impact of PostCond on sTRAIL in relationship to infarct size (area under the curve of Troponin T, AUCTnT) and left ventricle ejection fraction (LVEF) in a series of patients undergoing primary coronary intervention for ST-segment elevation myocardial infarction (STEMI). In a substudy of a randomized trial that tested the effects of PostCond in STEMI-patients, sTRAIL was measured 24 h after reperfusion (PostCond n = 39, Control n = 39). Correlations between sTRAIL and both AUCTnT and LVEF were studied for each study arm. At 24 h, sTRAIL was higher for PostCond vs Controls (46.4 ± 30.6 vs 32.9 ± 23.4, p = 0.031), was negatively related to AUCTnT [B = −0.09, 95 % CI (−0.15 to −0.30), p = 0.005] and was positively related to both in-hospital [B = 0.10, 95 % CI (0.02–0.17), p = 0.018], and follow-up LVEF [B = 0.21, 95 % (0.10–0.32), p = 0.001]. No significant relationship was found for Controls. On multivariate analysis, PostCond was an independent predictor for sTRAIL [B = 12.13 95 % CI (0.40–23.87), p = 0.043]. In conclusion, PostCond positively influenced sTRAIL, which was related to reduced infarct size and better LVEF. Further studies are needed to understand potential mechanisms elicited by PostCond in infarct size reduction.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Steg PG, James SK, Atar D, Badano LP, Blomstrom-Lundqvist C, Borger MA, Di Mario C, Dickstein K, Ducrocq G, Fernandez-Aviles F, Gershlick AH, Giannuzzi P, Halvorsen S, Huber K, Juni P, Kastrati A, Knuuti J, Lenzen MJ, Mahaffey KW, Valgimigli M, van ‘t Hof A, Widimsky P, Zahger D (2012) ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 33:2569–2619

    Article  CAS  PubMed  Google Scholar 

  2. Pedersen F, Butrymovich V, Kelbæk H, Wachtell K, Helqvist S, Kastrup J, Holmvang L, Clemmensen P, Engstrøm T, Grande P, Saunamäki K, Jørgensen E (2014) Short- and long-term cause of death in patients treated with primary PCI for STEMI. J Am Coll Cardiol 64:2101–2108

    Article  PubMed  Google Scholar 

  3. Miyachi H, Takagi A, Miyauchi K, Yamasaki M, Tanaka H, Yoshikawa M, Saji M, Suzuki M, Yamamoto T, Shimizu W, Nagao K, Takayama M (2016) Current characteristics and management of ST elevation and non-ST elevation myocardial infarction in the Tokyo metropolitan area: from the Tokyo CCU network registered cohort. Heart Vessels. doi:10.1007/s00380-015-0791-9

    PubMed  PubMed Central  Google Scholar 

  4. Prasad A, Stone GW, Holmes DR, Gersh B (2009) Reperfusion injury, microvascular dysfunction, and cardioprotection: the “dark side” of reperfusion. Circulation 120:2105–2112

    Article  PubMed  Google Scholar 

  5. Braunwald E, Kloner RA (1985) Myocardial reperfusion: a double-edged sword? J Clin Invest 76:1713–1719

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Yellon DM, Hausenloy DJ (2007) Myocardial reperfusion injury. N Engl J Med 357:1121–1135

    Article  CAS  PubMed  Google Scholar 

  7. Jennings RB (2013) Historical perspective on the pathology of myocardial ischemia/reperfusion injury. Circ Res 113:428–438

    Article  CAS  PubMed  Google Scholar 

  8. Kloner RA (2013) Current state of clinical translation of cardioprotective agents for acute myocardial infarction. Circ Res 113:451–463

    Article  CAS  PubMed  Google Scholar 

  9. Ndrepepa G (2015) Improving myocardial injury, infarct size, and myocardial salvage in the era of primary PCI for STEMI. Coron Artery Dis 26:341–355

    Article  PubMed  Google Scholar 

  10. Zhao ZQ, Corvera JS, Halkos ME, Kerendi F, Wang NP, Guyton RA, Vinten-Johansen J (2003) Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol 285:H579–H588

    Article  CAS  PubMed  Google Scholar 

  11. Khan AR, Binabdulhak AA, Alastal Y, Khan S, Faricy-Beredo BM, Luni FK, Lee WM, Khuder S, Tinkel J (2014) Cardioprotective role of ischemic postconditioning in acute myocardial infarction: a systematic review and meta-analysis. Am Heart J 168(512–521):e514

    Google Scholar 

  12. Favaretto E, Roffi M, Frigo AC, Lee MS, Marra MP, Napodano M, Tarantini G (2014) Meta-analysis of randomized trials of postconditioning in ST-elevation myocardial infarction. Am J Cardiol 114:946–952

    Article  PubMed  Google Scholar 

  13. Limalanathan S, Andersen GO, Klow NE, Abdelnoor M, Hoffmann P, Eritsland J (2014) Effect of ischemic postconditioning on infarct size in patients with ST-elevation myocardial infarction treated by primary PCI results of the POSTEMI (POstconditioning in ST-Elevation Myocardial Infarction) randomized trial. J Am Heart Assoc 3:e000679

    Article  PubMed  PubMed Central  Google Scholar 

  14. Eefting F, Rensing B, Wigman J, Pannekoek WJ, Liu WM, Cramer MJ, Lips DJ, Doevendans PA (2004) Role of apoptosis in reperfusion injury. Cardiovasc Res 61:414–426

    Article  CAS  PubMed  Google Scholar 

  15. Gottlieb RA, Burleson KO, Kloner RA, Babior BM, Engler RL (1994) Reperfusion injury induces apoptosis in rabbit cardiomyocytes. J Clin Invest 94:1621–1628

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Badalzadeh R, Mokhtari B, Yavari R (2015) Contribution of apoptosis in myocardial reperfusion injury and loss of cardioprotection in diabetes mellitus. J Physiol Sci 65:201–215

    Article  PubMed  Google Scholar 

  17. Freude B, Masters TN, Robicsek F, Fokin A, Kostin S, Zimmermann R, Ullmann C, Lorenz-Meyer S, Schaper J (2000) Apoptosis is initiated by myocardial ischemia and executed during reperfusion. J Mol Cell Cardiol 32:197–208

  18. Sasaki T, Shishido T, Kadowaki S, Kitahara T, Suzuki S, Katoh S, Funayama A, Netsu S, Watanabe T, Goto K, Takeishi Y, Kubota I (2014) Diacylglycerol kinase alpha exacerbates cardiac injury after ischemia/reperfusion. Heart Vessels 29:110–118

    Article  PubMed  Google Scholar 

  19. McCully JD, Wakiyama H, Hsieh YJ, Jones M, Levitsky S (2004) Differential contribution of necrosis and apoptosis in myocardial ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 286:H1923–H1935

    Article  CAS  PubMed  Google Scholar 

  20. Saraste A, Pulkki K, Kallajoki M, Henriksen K, Parvinen M, Voipio-Pulkki L-M (1997) Apoptosis in human acute myocardial infarction. Circulation 95:320–323

    Article  CAS  PubMed  Google Scholar 

  21. Biondi-Zoccai GG, Abbate A, Vasaturo F, Scarpa S, Santini D, Leone AM, Parisi Q, De Giorgio F, Bussani R, Silvestri F, Baldi F, Biasucci LM, Baldi A (2004) Increased apoptosis in remote non-infarcted myocardium in multivessel coronary disease. Int J Cardiol 94:105–110

    Article  PubMed  Google Scholar 

  22. Chen Z, Chua CC, Ho YS, Hamdy RC, Chua BH (2001) Overexpression of Bcl-2 attenuates apoptosis and protects against myocardial I/R injury in transgenic mice. Am J Physiol Heart Circ Physiol 280:H2313–H2320

    CAS  PubMed  Google Scholar 

  23. Rong F, Peng Z, Ye MX, Zhang QY, Zhao Y, Zhang SM, Guo HT, Hui B, Wang YM, Liang C, Gu CH, Tao C, Cui Q, Yu SQ, Yi DH, Pei JM (2009) Myocardial apoptosis and infarction after ischemia/reperfusion are attenuated by kappa-opioid receptor agonist. Arch Med Res 40:227–234

    Article  CAS  PubMed  Google Scholar 

  24. Lee P, Sata M, Lefer DJ, Factor SM, Walsh K, Kitsis RN (2003) Fas pathway is a critical mediator of cardiac myocyte death and MI during ischemia-reperfusion in vivo. Am J Physiol Heart Circ Physiol 284:H456–H463

    Article  CAS  PubMed  Google Scholar 

  25. Senturk T, Cavun S, Avci B, Yermezler A, Serdar Z, Savci V (2014) Effective inhibition of cardiomyocyte apoptosis through the combination of trimetazidine and N-acetylcysteine in a rat model of myocardial ischemia and reperfusion injury. Atherosclerosis 237:760–766

    Article  CAS  PubMed  Google Scholar 

  26. Nilsson L, Szymanowski A, Swahn E, Jonasson L (2013) Soluble TNF receptors are associated with infarct size and ventricular dysfunction in ST-elevation myocardial infarction. PLoS One 8:e55477

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Gan R, Hu G, Zhao Y, Li H, Jin Z, Ren H, Dong S, Zhong X, Li H, Yang B, Xu C, Lu F, Zhang W (2012) Post-conditioning protecting rat cardiomyocytes from apoptosis via attenuating calcium-sensing receptor-induced endo(sarco)plasmic reticulum stress. Mol Cell Biochem 361:123–134

    Article  CAS  PubMed  Google Scholar 

  28. Wagner C, Tillack D, Simonis G, Strasser RH, Weinbrenner C (2010) Ischemic post-conditioning reduces infarct size of the in vivo rat heart: role of PI3-K, mTOR, GSK-3beta, and apoptosis. Mol Cell Biochem 339:135–147

    Article  CAS  PubMed  Google Scholar 

  29. Ren Y, Cai Y, Jia D (2012) Comparative antiapoptotic effects of KB-R7943 and ischemic postconditioning during myocardial ischemia reperfusion. Cell Biochem Biophys 64:137–145

    Article  CAS  PubMed  Google Scholar 

  30. Zhao WS, Xu L, Wang LF, Zhang L, Zhang ZY, Liu Y, Liu XL, Yang XC, Cui L, Zhang L (2009) A 60-s postconditioning protocol by percutaneous coronary intervention inhibits myocardial apoptosis in patients with acute myocardial infarction. Apoptosis 14:1204–1211

    Article  PubMed  Google Scholar 

  31. Kimberley FC, Screaton GR (2004) Following a TRAIL: update on a ligand and its five receptors. Cell Res 14:359–372

    Article  CAS  PubMed  Google Scholar 

  32. Secchiero P, Corallini F, Ceconi C, Parrinello G, Volpato S, Ferrari R, Zauli G (2009) Potential prognostic significance of decreased serum levels of TRAIL after acute myocardial infarction. PLoS One 4:e4442

    Article  PubMed  PubMed Central  Google Scholar 

  33. Osmancik P, Teringova E, Tousek P, Paulu P, Widimsky P (2013) Prognostic value of TNF-related apoptosis inducing ligand (TRAIL) in acute coronary syndrome patients. PLoS One 8:e53860

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Luz A, Santos M, Magalhaes R, Silveira J, Cabral S, Dias V, Oliveira F, Pereira S, Leite-Moreira A, Carvalho H, Torres S (2015) Lack of benefit of ischemic PostConditioning after routine thrombus aspiration during reperfusion: immediate and midterm results. J Cardiovasc Pharmacol Ther 20:523–531

    Article  PubMed  Google Scholar 

  35. Morrow DA, Antman EM, Charlesworth A, Cairns R, Murphy SA, de Lemos JA, Giugliano RP, McCabe CH, Braunwald E (2000) TIMI risk score for ST-elevation myocardial infarction: a convenient, bedside, clinical score for risk assessment at presentation: An intravenous nPA for treatment of infracting myocardium early II trial substudy. Circulation 102:2031–2037

    Article  CAS  PubMed  Google Scholar 

  36. Brandt PW, Partridge JB, Wattie WJ (1977) Coronary arteriography; method of presentation of the arteriogram report and a scoring system. Clin Radiol 28:361–365

    Article  CAS  PubMed  Google Scholar 

  37. Graham MM, Faris PD, Ghali WA, Galbraith PD, Norris CM, Badry JT, Mitchell LB, Curtis MJ, Knudtson ML (2001) Validation of three myocardial jeopardy scores in a population-based cardiac catheterization cohort. Am Heart J 142:254–261

    Article  CAS  PubMed  Google Scholar 

  38. Ortiz-Perez JT, Meyers SN, Lee DC, Kansal P, Klocke FJ, Holly TA, Davidson CJ, Bonow RO, Wu E (2007) Angiographic estimates of myocardium at risk during acute myocardial infarction: validation study using cardiac magnetic resonance imaging. Eur Heart J 28:1750–1758

    Article  PubMed  Google Scholar 

  39. Sianos G, Morel MA, Kappetein AP, Morice MC, Colombo A, Dawkins K, van den Brand M, Van Dyck N, Russell ME, Mohr FW, Serruys PW (2005) The SYNTAX Score: an angiographic tool grading the complexity of coronary artery disease. EuroIntervention 1:219–227

    PubMed  Google Scholar 

  40. Lee Y, Gustafsson AB (2009) Role of apoptosis in cardiovascular disease. Apoptosis 14:536–548

    Article  PubMed  Google Scholar 

  41. Secchiero P, Candido R, Corallini F, Zacchigna S, Toffoli B, Rimondi E, Fabris B, Giacca M, Zauli G (2006) Systemic tumor necrosis factor-related apoptosis-inducing ligand delivery shows antiatherosclerotic activity in apolipoprotein E-null diabetic mice. Circulation 114:1522–1530

    Article  CAS  PubMed  Google Scholar 

  42. Liu M, Xiang G, Lu J, Xiang L, Dong J, Mei W (2014) TRAIL protects against endothelium injury in diabetes via Akt-eNOS signaling. Atherosclerosis 237:718–724

    Article  CAS  PubMed  Google Scholar 

  43. Toffoli B, Bernardi S, Candido R, Zacchigna S, Fabris B, Secchiero P (2012) TRAIL shows potential cardioprotective activity. Invest New Drugs 30:1257–1260

    Article  CAS  PubMed  Google Scholar 

  44. Kavurma MM, Schoppet M, Bobryshev YV, Khachigian LM, Bennett MR (2008) TRAIL stimulates proliferation of vascular smooth muscle cells via activation of NF-kappaB and induction of insulin-like growth factor-1 receptor. J Biol Chem 283:7754–7762

    Article  CAS  PubMed  Google Scholar 

  45. Secchiero P, Zerbinati C, Rimondi E, Corallini F, Milani D, Grill V, Forti G, Capitani S, Zauli G (2004) TRAIL promotes the survival, migration and proliferation of vascular smooth muscle cells. Cell Mol Life Sci 61:1965–1974

    Article  CAS  PubMed  Google Scholar 

  46. Richter B, Koller L, Hohensinner PJ, Zorn G, Brekalo M, Berger R, Mortl D, Maurer G, Pacher R, Huber K, Wojta J, Hulsmann M, Niessner A (2013) A multi-biomarker risk score improves prediction of long-term mortality in patients with advanced heart failure. Int J Cardiol 168:1251–1257

    Article  PubMed  Google Scholar 

  47. Volpato S, Ferrucci L, Secchiero P, Corallini F, Zuliani G, Fellin R, Guralnik JM, Bandinelli S, Zauli G (2011) Association of tumor necrosis factor-related apoptosis-inducing ligand with total and cardiovascular mortality in older adults. Atherosclerosis 215:452–458

    Article  CAS  PubMed  Google Scholar 

  48. Mori K, Ikari Y, Jono S, Shioi A, Ishimura E, Emoto M, Inaba M, Hara K, Nishizawa Y (2010) Association of serum TRAIL level with coronary artery disease. Thromb Res 125:322–325

    Article  CAS  PubMed  Google Scholar 

  49. Deftereos S, Giannopoulos G, Panagopoulou V, Raisakis K, Kossyvakis C, Kaoukis A, Tzalamouras V, Mavri M, Pyrgakis V, Cleman MW, Stefanadis C (2012) Inverse association of coronary soluble tumor necrosis factor-related apoptosis inducing ligand (sTRAIL) levels to in-stent neointimal hyperplasia. Cardiology 123:97–102

    Article  CAS  PubMed  Google Scholar 

  50. Deftereos S, Giannopoulos G, Kossyvakis C, Kaoukis A, Raisakis K, Panagopoulou V, Miliou A, Theodorakis A, Driva M, Pyrgakis V, Stefanadis C, Cleman MW (2012) Association of soluble tumour necrosis factor-related apoptosis-inducing ligand levels with coronary plaque burden and composition. Heart 98:214–218

    Article  CAS  PubMed  Google Scholar 

  51. Secchiero P, Gonelli A, Corallini F, Ceconi C, Ferrari R, Zauli G (2010) Metalloproteinase 2 cleaves in vitro recombinant TRAIL: potential implications for the decreased serum levels of TRAIL after acute myocardial infarction. Atherosclerosis 211:333–336

    Article  CAS  PubMed  Google Scholar 

  52. Nakajima H, Yanase N, Oshima K, Sasame A, Hara T, Fukazawa S, Takata R, Hata K, Mukai K, Yamashina A, Mizuguchi J (2003) Enhanced expression of the apoptosis inducing ligand TRAIL in mononuclear cells after myocardial infarction. Jpn Heart J 44:833–844

    Article  CAS  PubMed  Google Scholar 

  53. Zauli G, Pandolfi A, Gonelli A, Di Pietro R, Guarnieri S, Ciabattoni G, Rana R, Vitale M, Secchiero P (2003) Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) sequentially upregulates nitric oxide and prostanoid production in primary human endothelial cells. Circ Res 92:732–740

    Article  CAS  PubMed  Google Scholar 

  54. Cheng W, Zhao Y, Wang S, Jiang F (2014) Tumor necrosis factor-related apoptosis-inducing ligand in vascular inflammation and atherosclerosis: a protector or culprit? Vascul Pharmacol 63:135–144

    Article  CAS  PubMed  Google Scholar 

  55. Forde H, Harper E, Davenport C, Rochfort KD, Wallace R, Murphy RP, Smith D, Cummins PM (2016) The beneficial pleiotropic effects of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) within the vasculature: a review of the evidence. Atherosclerosis 247:87–96

    Article  CAS  PubMed  Google Scholar 

  56. Luz A, Santos M, Rodrigues P, Sousa MJ, Anjo D, Silveira I, Brochado B, Silveira J, Cabral S, Leite-Moreira A, Carvalho H, Torres S (2015) Preinfarction angina: clinical significance and relationship with total ischemic time in patients with ST-elevation myocardial infarction. Coron Artery Dis 26:22–29

    Article  PubMed  Google Scholar 

  57. Hausenloy DJ, Yellon DM (2007) Preconditioning and postconditioning: united at reperfusion. Pharmacol Ther 116:173–191

    Article  CAS  PubMed  Google Scholar 

  58. Wang L, Li X, Zhou Y, Shi H, Xu C, He H, Wang S, Xiong X, Zhang Y, Du Z, Zhang R, Lu Y, Yang B, Shan H (2014) Downregulation of miR-133 via MAPK/ERK signaling pathway involved in nicotine-induced cardiomyocyte apoptosis. Naunyn Schmiedebergs Arch Pharmacol 387:197–206

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank all the medical, technical and nursing staff belonging to the Cardiology and Laboratory departments for their support.

Author information

Authors and Affiliations

  1. Cardiology Department, Centro Hospitalar do Porto, Largo Prof. Abel Salazar 4099-001, Porto, Portugal

    André Luz, Mário Santos, João Silveira, Sofia Cabral, Severo Torres & Henrique Carvalho

  2. Clinical Chemistry Department, Centro Hospitalar do Porto, Porto, Portugal

    José Carlos Oliveira & Ana Pacheco

  3. Institute of Biomedical Sciences of “Abel Salazar” (ICBAS), University of Porto, Porto, Portugal

    Rui Magalhães, José Carlos Oliveira, João Silveira, Severo Torres & Henrique Carvalho

  4. Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine (FMUP), University of Porto, Porto, Portugal

    Mário Santos & Adelino F. Leite-Moreira

Authors
  1. André Luz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mário Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rui Magalhães
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. José Carlos Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ana Pacheco
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. João Silveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sofia Cabral
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Severo Torres
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Adelino F. Leite-Moreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Henrique Carvalho
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to André Luz.

Ethics declarations

Conflict of interest

The authors have no conflicts of interest to disclose regarding this paper.

Funding

This work was funded by Porto Hospital Centre and by Medtronic Portugal.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Luz, A., Santos, M., Magalhães, R. et al. Soluble TNF-related apoptosis induced ligand (sTRAIL) is augmented by Post-Conditioning and correlates to infarct size and left ventricle dysfunction in STEMI patients: a substudy from a randomized clinical trial. Heart Vessels 32, 117–125 (2017). https://doi.org/10.1007/s00380-016-0851-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00380-016-0851-9

Keywords

Search

Navigation