Skip to main content
Log in

Myocardial preconditioning and remote renal preconditioning

Identifying a protective factor using proteomic methods?

  • ORIGINAL CONTRIBUTION
  • Published:
Basic Research in Cardiology Aims and scope Submit manuscript

Abstract

It is still unknown whether remote ischemic preconditioning is mediated by a humoral or a neurogenic mechanism from the preconditioning to the preconditioned tissue. The purpose of the following study was to identify a possible humoral trigger of ischemic myocardial preconditioning and remote renal preconditioning. Open chest rats were subjected to a coronary artery occlusion period of 45 min followed by 2 h of reperfusion (Control animals; n = 6). The coronary preconditioned group (IPC, n = 6) was subjected to a preceding preconditioning period of 5 min coronary artery occlusion followed by 5 min of reperfusion, repeated three times. The renal preconditioned group (IPR, n = 6) was subjected to a preceding renal artery occlusion period of 10 min followed by 20 min of reperfusion. Area at risk (AAR) and infarcted area (IA) were determined at the end of each protocol. Blood samples were taken at the end of the preconditioning protocols from parallel experiments for proteomic analysis using two–dimensional gel electrophoresis (2-DE), matrix assisted laser desorption and ionization—time of flight—mass spectrometry (MALDI–TOF–MS), and liquid chromatography—electrospray ionization—tandem mass spectrometry (nanoLC–ESI–MS/MS). IA/AAR was 87.8 ± 10.7% in the control group. IPC and IPR signi.cantly reduced IA/AAR (58.2 ± 9.3% and 56.9 ± 9.0%, p < 0.001). Proteomic analyses detected four protein spots which were either up– (n = 3) or down–regulated in the preconditioned groups vs. the control group. The three up–regulated protein spots were identi.ed as albumin fragments, whereas the downregulated spot was identified as liver regeneration–related protein (LRRG03). Interestingly, albumin modification by brief ischemia has been recently shown and evaluated for the clinical diagnosis of sublethal myocardial ischemia. However, no differentially abundant proteins which possess a known signaling function could be found. Hence, though there is a differential protein expression in blood following IPC and IPR, our data are not in favor of a humoral mediator of remote preconditioning with a molecular weight of more than 8 kDa. Our results rather suggest either a neurogenic pathway or a mediator smaller than 8 kDa.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Aitchison KA, Baxter GF, Awan MM, Smith RM, Yellon DM, Opie LH (2000) Opposing effects on infarction of delta and kappa opioid receptor activation in the isolated rat heart: implications for ischemic preconditioning. Basic Res Cardiol 95:1–10

    Article  CAS  PubMed  Google Scholar 

  2. Bar Or D, Winkler JV, Vanbenthuysen K, Harris L, Lau E, Hetzel FW (2001) Reduced albumin-cobalt binding with transient myocardial ischemia after elective percutaneous transluminal coronary angioplasty: a preliminary comparison to creatine kinase-MB, myoglobin, and troponin I. Am Heart J 141:985–991

    CAS  Google Scholar 

  3. Birnbaum Y, Hale SL, Kloner RA (1997) Ischemic preconditioning at a distance: reduction of myocardial infarct size by partial reduction of blood supply combined with rapid stimulation of the gastrocnemius muscle in the rabbit. Circulation 96:1641–1646

    Google Scholar 

  4. Chien GL, Mohtadi K, Wolff RA, Van Winkle DM (1999) Naloxone blockade of myocardial ischemic preconditioning does not require central nervous system participation. Basic Res Cardiol 94:136–143

    Article  CAS  PubMed  Google Scholar 

  5. Christenson RH, Duh SH, Sanhai WR, Wu AH, Holtman V, Painter P, Branham E, Apple FS, Murakami M, Morris DL (2001) Characteristics of an Albumin Cobalt Binding Test for assessment of acute coronary syndrome patients: a multicenter study. Clin Chem 47:464–470

    CAS  PubMed  Google Scholar 

  6. Dickson EW, Lorbar M, Porcaro WA, Fenton RA, Reinhardt CP, Gysembergh A, Przyklenk K (1999) Rabbit heart can be “preconditioned” via transfer of coronary ef.uent. Am J Physiol 277:H2451–H2457

    CAS  PubMed  Google Scholar 

  7. Doherty NS, Littman BH, Reilly K, Swindell AC, Buss JM, Anderson NL (1998) Analysis of changes in acute-phase plasma proteins in an acute in.ammatory response and in rheumatoid arthritis using two-dimensional gel electrophoresis. Electrophoresis 19:355–363

    Article  CAS  PubMed  Google Scholar 

  8. Downey JM, Cohen MV (1996) Preconditioning: markers vs. epiphenomena. Basic Res Cardiol 91:35–37

    CAS  PubMed  Google Scholar 

  9. Gho BC, Schoemaker RG, van den Doel MA, Duncker DJ, Verdouw PD (1996) Myocardial protection by brief ischemia in noncardiac tissue. Circulation 94:2193–200

    CAS  PubMed  Google Scholar 

  10. Gross GJ (1995) ATP-sensitive potassium channels and myocardial preconditioning. Basic Res Cardiol 90:85–88

    CAS  PubMed  Google Scholar 

  11. Heusch G, Schulz R (2002) Remote preconditioning. J Mol Cell Cardiol 34:1279–1281

    Article  CAS  PubMed  Google Scholar 

  12. Jungblut PR, Seifert R (1990) Analysis by high-resolution two-dimensional electrophoresis of differentiation-dependent alterations in cytosolic protein pattern of HL-60 leukemic cells. J Biochem Biophys Methods 21:47–58

    Article  CAS  PubMed  Google Scholar 

  13. Kloner RA, Jennings RB (2001) Consequences of brief ischemia: stunning, preconditioning, and their clinical implications: part 1. Circulation 104:2981–2989

    CAS  PubMed  Google Scholar 

  14. Kloner RA, Jennings RB (2001) Consequences of brief ischemia: stunning, preconditioning, and their clinical implications: part 2. Circulation 104:3158–167

    CAS  PubMed  Google Scholar 

  15. Klose J, Kobalz U (1995) Two-dimensional electrophoresis of proteins: an updated protocol and implications for a functional analysis of the genome. Electrophoresis 16:1034–1059

    Article  CAS  PubMed  Google Scholar 

  16. Konstantinov IE, Li J, Cheung MM, Shimizu M, Stokoe J, Kharbanda RK, Redington AN (2005) Remote ischemic preconditioning of the recipient reduces myocardial ischemia-reperfusion injury of the denervated donor heart via a Katp channel-dependent mechanism. Transplantation 79:1691–1695

    Article  PubMed  Google Scholar 

  17. Kristiansen SB, Henning O, Kharbanda RK, Nielsen Kudsk JE, Schmidt MR, Redington AN, Nielsen TT, Botker HE (2005) Remote preconditioning reduces ischemic injury in the explanted heart by a KATP channel-dependent mechanism. Am J Physiol Heart Circ Physiol 288: H1252–H1256

    CAS  PubMed  Google Scholar 

  18. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685

    Article  CAS  PubMed  Google Scholar 

  19. Liauw SK, Rubin BB, Lindsay TF, Romaschin AD, Walker PM (1996) Sequential ischemia/reperfusion results in contralateral skeletal muscle salvage. Am J Physiol 270:H1407–H413

    CAS  PubMed  Google Scholar 

  20. Manthei SA, Van Wylen DG (1997) Purine metabolite accumulation during myocardial ischemia: adenosine pretreatment versus brief ischemia. Basic Res Cardiol 92:368–377

    CAS  PubMed  Google Scholar 

  21. McClanahan T, Nao B, Wolke L, Martin B, Mertz T, Gallagher K (1993) Brief renal occlusion and reperfusion reduces myocardial infarct size in rabbits. FASEB J 7:A118 (Abstract)

    Google Scholar 

  22. Miura T (1996) Adenosine and bradykinin: are they independent triggers of preconditioning? Basic Res Cardiol 91:20–22

    Article  CAS  PubMed  Google Scholar 

  23. Murry CE, Jennings RB, Reimer KA (1986) Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74:1124–1136

    CAS  PubMed  Google Scholar 

  24. Nakano A, Heusch G, Cohen MV, Downey JM (2002) Preconditioning one myocardial region does not neccessarily precondition the whole rabbit heart. Basic Res Cardiol 97:35–39

    Article  PubMed  Google Scholar 

  25. Pell TJ, Baxter GF, Yellon DM, Drew GM (1998) Renal ischemia preconditions myocardium: role of adenosine receptors and ATP-sensitive potassium channels. Am J Physiol 275:H1542–H1547

    CAS  PubMed  Google Scholar 

  26. Piper HM, Ladilov YV (1997) Ischemic preconditioning on the cellular level. Basic Res Cardiol 92 Suppl 2:32–33

    PubMed  Google Scholar 

  27. Przyklenk K, Bauer B, Ovize M, Kloner RA, Whittaker P (1993) Regional ischemic ‘preconditioning’ protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation 87:893–899

    CAS  PubMed  Google Scholar 

  28. Przyklenk K, Darling CE, Dickson EW, Whittaker P (2003) Cardioprotection ‘outside the box’ – the evolving paradigm of remote preconditioning. Basic Res Cardiol 98:149–157

    PubMed  Google Scholar 

  29. Przyklenk K, Kloner RA (1996) Role of protein kinase C in ischemic preconditioning: in search of the “pure and simple truth”. Basic Res Cardiol 91:41–43

    CAS  PubMed  Google Scholar 

  30. Rohmann S, Weygandt H, Schelling P, Kie Soei L, Verdouw PD, Lues I (1994) Involvement of ATP-sensitive potassium channels in preconditioning protection. Basic Res Cardiol 89:563–576

    Article  CAS  PubMed  Google Scholar 

  31. Steenbergen C (2002) The role of p38 mitogen-activated protein kinase in myocardial ischemia/reperfusion injury; relationship to ischemic preconditioning. Basic Res Cardiol 97:276–285

    Article  CAS  PubMed  Google Scholar 

  32. Takaoka A, Nakae I, Mitsunami K, Yabe T, Morikawa S, Inubushi T, Kinoshita M (1999) Renal ischemia/reperfusion remotely improves myocardial energy metabolism during myocardial ischemia via adenosine receptors in rabbits: effects of “remote preconditioning”. J Am Coll Cardiol 33:556–564

    Article  CAS  PubMed  Google Scholar 

  33. Verdouw PD, van den Doel MA, de Zeeuw S, Duncker DJ (1997) On the relevance of ischemic preconditioning in humans. Basic Res Cardiol 92 Suppl 2:51–53

    PubMed  Google Scholar 

  34. Weinbrenner C, Nelles M, Herzog N, Sarvary L, Strasser RH (2002) Remote preconditioning by infrarenal occlusion of the aorta protects the heart from infarction: a newly identified non-neuronal but PKC-dependent pathway. Cardiovasc Res 55:590–601

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A. M. Vogt.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lang, S.C., Elsässer, A., Scheler, C. et al. Myocardial preconditioning and remote renal preconditioning. Basic Res Cardiol 101, 149–158 (2006). https://doi.org/10.1007/s00395-005-0565-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00395-005-0565-0

Key words

Navigation