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Osteopontin protects against cardiac ischemia-reperfusion injury through late preconditioning

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Abstract

Osteopontin (OPN) has been considered as a proinflammatory cytokine. A protective role for OPN in ischemic injury was demonstrated recently. Because proinflammatory cytokines play an important role in induction of late preconditioning, we deduce that OPN may induce late preconditioning in myocardium. Fifty consecutive patients scheduled for mitral valve replacement (MVR) were investigated. Osteopontin and high-sensitivity Creactive protein levels in plasma before surgery were determined. Nuclear factor kappa B and signal transducer and activator of transcription 3 (STAT3), two main transcription factors involved in late preconditioning, were investigated by electrophoretic mobility shift assay. The effector proteins in late preconditioning, including inducible nitric oxide synthase and cyclooxygenase-2, were evaluated by immunoblotting. Cardioprotective effects were assessed by creatine kinase MB (CK-MB) and cardiac troponin T (cTnT) leakage postoperatively. The protective effects of OPN on neonatal cardiomyocytes against anoxia-reoxygenation-induced injury were also tested. The protein synthesis inhibitor cycloheximide (CH) was used in this model to test if new protein synthesis was necessary for its cardioprotective effects. There was no perioperative death in the groups. We found that patients with higher plasma OPN levels (167 ± 35 ng/ml vs 63 ± 13 ng/ml) had more activated extent of transcription factors, higher expression of effector proteins, and better cardioprotective effects, assessed by CK-MB and cTnT. An in vitro experiment also revealed that OPN had a cardioprotective effect 24 h after pretreatment. However, the protective effect was blocked by the protein synthesis inhibitor CH. Osteopontin can protect against cardiac ischemia-reperfusion injury through late preconditioning.

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References

  1. Weber GF, Cantor H (1996) The immunology of Eta-1/osteopontin. Cytokine Growth Factor Rev 7:241–248

    Article  PubMed  CAS  Google Scholar 

  2. Yu XQ, Nikolic-Paterson DJ, Mu W, Giachelli CM, Atkins RC, Johnson RJ, Lan HY (1998) A functional role for osteopontin in experimental crescentic glomerulonephritis in the rat. Proc Assoc Am Physicians 110:50–64

    PubMed  CAS  Google Scholar 

  3. Ashkar S, Weber GF, Panoutsakopoulou V, Sanchirico ME, Jansson M, Zawaideh S, Rittling SR, Denhardt DT, Glimcher MJ, Cantor H (2000) Eta-1 (osteopontin): an early component of type-1 (cell-mediated) immunity. Science 287:860–864

    Article  PubMed  CAS  Google Scholar 

  4. Buxton DB (2004) Cytokines and late preconditioning. Cardiovasc Res 64:6–8

    Article  PubMed  CAS  Google Scholar 

  5. Hoshida S, Yamashita N, Otsu K, Hori M (2002) The importance of manganese superoxide dismutase in delayed preconditioning: involvement of reactive oxygen species and cytokines. Cardiovasc Res 55:495–505

    Article  PubMed  CAS  Google Scholar 

  6. Hoshida S, Yamashita N, Otsu K, Hori M (2002) Repeated physiologic stresses provide persistent cardioprotection against ischemia-reperfusion injury in rats. J Am Coll Cardiol 40:826–831

    Article  PubMed  Google Scholar 

  7. Padanilam BJ, Martin DR, Hammerman MR (1996) Insulin-like growth factor I-enhanced renal expression of osteopontin after acute ischemic injury in rats. Endocrinology 137:2133–2140

    Article  PubMed  CAS  Google Scholar 

  8. Persy VP, Verstrepen WA, Ysebaert DK, De Greef KE, De Broe ME (1999) Differences in osteopontin up-regulation between proximal and distal tubules after renal ischemia/reperfusion. Kidney Int 56:601–611

    Article  PubMed  CAS  Google Scholar 

  9. Meller R, Stevens SL, Minami M, Cameron JA, King S, Rosenzweig H, Doyle K, Lessov NS, Simon RP, Stenzel-Poore MP (2005) Neuroprotection by osteopontin in stroke. J Cereb Blood Flow Metab 25:217–225

    Article  PubMed  CAS  Google Scholar 

  10. Brady PA, Terzic A (1998) The sulfonylurea controversy: more questions from the heart. J Am Coll Cardiol 31:950–956

    Article  PubMed  CAS  Google Scholar 

  11. Ishihara M, Sato H, Tateishi H, Kawagoe T, Shimatani Y, Ueda K, Noma K, Yumoto A, Nishioka K (2000) Beneficial effect of prodromal angina pectoris is lost in elderly patients with acute myocardial infarction. Am Heart J 139:881–888

    Article  PubMed  CAS  Google Scholar 

  12. Atalar E, Ozturk E, Ozer N, Kepez A, Coskun S, Aksoyek S, Ovunc K, Kes S, Kirazli S, Ozmen F (2006) Plasma soluble osteopontin concentrations are increased in patients with rheumatic mitral stenosis and associated with the severity of mitral valve calcium. Am J Cardiol 98:817–820

    Article  PubMed  CAS  Google Scholar 

  13. Wang Y, Yin B, Liu S, Xue S (2007) Cardioprotective effect by tumor necrosis factor-alpha and interleukin-6 through late preconditioning in unstable angina patients. Arch Med Res 38:80–85

    Article  PubMed  CAS  Google Scholar 

  14. Rajamannan NM, Nealis TB, Subramaniam M, Pandya S, Stock SR, Ignatiev CI, Sebo TJ, Rosengart TK, Edwards WD, McCarthy PM, Bonow RO, Spelsberg TC (2005) Calcified rheumatic valve neoangiogenesis is associated with vascular endothelial growth factor expression and osteoblast-like bone formation. Circulation 111:3296–3301

    Article  PubMed  CAS  Google Scholar 

  15. Soejima H, Irie A, Fukunaga T, Sugamura K, Kojima S, Sakamoto T, Yoshimura M, Kishikawa H, Nishimura Y, Ogawa H (2006) Elevated plasma osteopontin levels were associated with osteopontin expression of CD4+ T cells in patients with unstable angina. Circ J 70:851–856

    Article  PubMed  CAS  Google Scholar 

  16. Pasqui AL, Di Renzo M, Auteri A, Puccetti L (2005) Cytokines in acute coronary syndromes. Int J Cardiol 105:355–336

    Article  PubMed  CAS  Google Scholar 

  17. Giannitsis E, Steen H, Kurz K, Ivandic B, Simon AC, Futterer S, Schild C, Isfort P, Jaffe AS, Katus HA (2008) Cardiac magnetic resonance imaging study for quantification of infarct size comparing directly serial versus single time-point measurements of cardiac troponin T. J Am Coll Cardiol 51:307–314

    Article  PubMed  CAS  Google Scholar 

  18. Hedstrom E, Astrom-Olsson K, Ohlin H, Frogner F, Carlsson M, Billgren T, Jovinge S, Cain P, Wagner GS, Arheden H (2007) Peak CKMB and cTnT accurately estimates myocardial infarct size after reperfusion. Scand Cardiovasc J 41:44–50

    Article  PubMed  Google Scholar 

  19. Yesilbursa D, Serdar A, Senturk T, Serdar Z, Sag S, Cordan J (2006) Effect of N-acetylcysteine on oxidative stress and ventricular function in patients with myocardial infarction. Heart Vessels 21:33–37

    Article  PubMed  Google Scholar 

  20. Cheng L, Ma S, Wei LX (2007) Cardioprotective and antiarrhythmic effect of U50,488H in ischemia/reperfusion rat heart. Heart Vessels 22:335–344

    Article  PubMed  Google Scholar 

  21. Lochner A, Genade S, Moolman JA (2003) Ischemic preconditioning: infarct size is a more reliable endpoint than functional recovery. Basic Res Cardiol 98:337–346

    Article  PubMed  CAS  Google Scholar 

  22. Bolli R (2000) The late phase of preconditioning. Circ Res 87:972–983

    PubMed  CAS  Google Scholar 

  23. Rizvi A, Tang XL, Qiu Y, Xuan YT, Takano H, Jadoon AK, Bolli R (1999) Increased protein synthesis is necessary for the development of late preconditioning against myocardial stunning. Am J Physiol 277(3 Pt 2): H874–H884

    PubMed  CAS  Google Scholar 

  24. Xuan YT, Tang XL, Banerjee S, Takano H, Li RC, Han H, Qiu Y, Li JJ, Bolli R (1999) Nuclear factor-kappaB plays an essential role in the late phase of ischemic preconditioning in conscious rabbits. Circ Res 84:1095–1109

    PubMed  CAS  Google Scholar 

  25. Xuan YT, Guo Y, Han H, Zhu Y, Bolli R (2001) An essential role of the JAK-STAT pathway in ischemic preconditioning. Proc Natl Acad Sci USA 98:9050–9055

    Article  PubMed  CAS  Google Scholar 

  26. Dawn B, Xuan YT, Guo Y, Rezazadeh A, Stein AB, Hunt G, Wu WJ, Tan W, Bolli R (2004) IL-6 plays an obligatory role in late preconditioning via JAK-STAT signaling and upregulation of iNOS and COX-2. Cardiovasc Res 64:61–71

    Article  PubMed  CAS  Google Scholar 

  27. Meng X, Cleveland JC, Rowland RT, Mitchell MB, Brown JM, Banerjee A, Harken AH (1996) Norepinephrine-induced sustained myocardial adaptation to ischemia is dependent on alpha 1-adrenoceptors and protein synthesis. J Mol Cell Cardiol 28:2017–2025

    Article  PubMed  CAS  Google Scholar 

  28. Das R, Mahabeleshwar GH, Kundu GC (2003) Osteopontin stimulates cell motility and nuclear factor kappaB-mediated secretion of urokinase type plasminogen activator through phosphatidylinositol 3-kinase/Akt signaling pathways in breast cancer cells. J Biol Chem 278:28593–28606

    Article  PubMed  CAS  Google Scholar 

  29. Zheng DQ, Woodard AS, Tallini G, Languino LR (2000) Substrate specificity of alpha(v)beta(3) integrin-mediated cell migration and phosphatidylinositol 3-kinase/AKT pathway activation. J Biol Chem 275:24565–24574

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Cardiovascular Surgery, RenJi Hospital of Shanghai Jiaotong University, Shanghai, 200127, PR China

    Yongyi Wang, Dafu Shen & Song Xue

  2. Department of Cardiothoracic Surgery, TaiZhou Hospital of Wenzhou Medical College, Linhai, Zhejiang, PR China

    Baofu Chen

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  1. Yongyi Wang
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  2. Baofu Chen
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  4. Song Xue
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Correspondence to Song Xue.

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The first two authors contributed equally to this work.

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Wang, Y., Chen, B., Shen, D. et al. Osteopontin protects against cardiac ischemia-reperfusion injury through late preconditioning. Heart Vessels 24, 116–123 (2009). https://doi.org/10.1007/s00380-008-1094-1

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  • DOI: https://doi.org/10.1007/s00380-008-1094-1

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