Hypoxia-inducible factor 1-alpha release after intracoronary versus intramyocardial stem cell therapy in myocardial infarction

Mariann Gyöngyösi, Rayyan Hemetsberger, Aniko Posa, Silvia Charwat, Noemi Pavo, Örs Petnehazy, Zsolt Petrasi, Imre J. Pavo, Hani Hemetsberger, Imre Benedek, Teodora Benedek, Istvan Benedek, Istvan Kovacs, Christoph Kaun, Gerald Maurer

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11 Citations (Scopus)

Abstract

We have investigated the effect of stem cell delivery on the release of hypoxia-inducible factor 1 alpha (HIF-1α) in peripheral circulation and myocardium in experimental myocardial ischemia. Closed-chest, reperfused myocardial infarction (MI) was created in domestic pigs. Porcine mesenchymal stem cells (MSCs) were cultured and delivered (9.8±1.2×10 6) either percutaneously NOGAguided transendocardially (Group IM) or intracoronary (Group IC) 22±4 days post-MI. Pigs without MSC delivery served as sham control (Group S). Plasma HIF-1α was measured at baseline, immediately post-and at follow-up (FUP; 2 h or 24 h) post-MSC delivery by ELISA kit. Myocardial HIF-1α expression of infarcted, normal myocardium, or border zone was determined by Western blot. Plasma level of HIF-1α increased immediately post-MI (from 278±127 to 631±375 pg/ml, p<0.05). Cardiac delivery of MSCs elevated the plasma levels of HIF-1α significantly (p lt;0.05) in groups IC and IM immediately post-MSC delivery, and returned to baseline level at FUP, without difference between the groups IC and IM. The myocardial tissue HIF-1α expression in the infarcted area was higher in Group IM than in Group IC or S (1,963±586 vs. 1,307±392 vs. 271±110 activity per square millimeter, respectively, p<0.05), while the border zone contained similarly lower level of HIF-1α, but still significantly higher as compared with Group S. Trend towards increase in myocardial expression of HIF-1α was measured in Group IM at 24 h, in contrast to Group IC. In conclusion, both stem cell delivery modes increase the systemic and myocardial level of HIF-1α. Intramyocardial delivery of MSC seems to trigger the release of angiogenic HIF-1α more effectively than does intracoronary delivery.

Original languageEnglish
Pages (from-to)114-121
Number of pages8
JournalJournal of Cardiovascular Translational Research
Volume3
Issue number2
DOIs
Publication statusPublished - Apr 2010

Keywords

  • Cardiac delivery
  • Hypoxia-inducible factor 1 alpha
  • Myocardial infarction
  • Stem cell

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmaceutical Science
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

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  • Cite this

    Gyöngyösi, M., Hemetsberger, R., Posa, A., Charwat, S., Pavo, N., Petnehazy, Ö., Petrasi, Z., Pavo, I. J., Hemetsberger, H., Benedek, I., Benedek, T., Benedek, I., Kovacs, I., Kaun, C., & Maurer, G. (2010). Hypoxia-inducible factor 1-alpha release after intracoronary versus intramyocardial stem cell therapy in myocardial infarction. Journal of Cardiovascular Translational Research, 3(2), 114-121. https://doi.org/10.1007/s12265-009-9154-1