Hypoxia-inducible factor 1-alpha release after intracoronary versus intramyocardial stem cell therapy in myocardial infarction.
We have investigated the effect of stem cell delivery on the release of hypoxia-inducible factor 1 alpha (HIF-1alpha) 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 x 10(6)) either percutaneously NOGA-guided transendocardially (Group IM) or intracoronary (Group IC) 22 +/- 4 days post-MI. Pigs without MSC delivery served as sham control (Group S). Plasma HIF-1alpha was measured at baseline, immediately post- and at follow-up (FUP; 2 h or 24 h) post-MSC delivery by ELISA kit. Myocardial HIF-1alpha expression of infarcted, normal myocardium, or border zone was determined by Western blot. Plasma level of HIF-1alpha 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-1alpha significantly (p < 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-1alpha 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-1alpha, but still significantly higher as compared with Group S. Trend towards increase in myocardial expression of HIF-1alpha 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-1alpha. Intramyocardial delivery of MSC seems to trigger the release of angiogenic HIF-1alpha more effectively than does intracoronary delivery.
Gyöngyösi
Mariann
M
Department of Cardiology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria. mariann.gyongyosi@meduniwien.ac.at
Hemetsberger
Rayyan
R
Posa
Aniko
A
Charwat
Silvia
S
Pavo
Noemi
N
Petnehazy
Ors
O
Petrasi
Zsolt
Z
Pavo
Imre J
IJ
Hemetsberger
Hani
H
Benedek
Imre
I
Benedek
Teodora
T
Benedek
Istvan
I
Kovacs
Istvan
I
Kaun
Christoph
C
Maurer
Gerald
G
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000097:blood / Q000378:metabolism*; D007267:Injections; D045164:Mesenchymal Stem Cell Transplantation; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D034421:Sus scrofa; D013997:Time Factors; D015854:Up-Regulation; D016277:Ventricular Function, Left
D051795:Hypoxia-Inducible Factor 1, alpha Subunit