, Volume 3, Issue 2, pp 114-121
Date: 23 Dec 2009

Hypoxia-Inducible Factor 1-Alpha Release After Intracoronary Versus Intramyocardial Stem Cell Therapy in Myocardial Infarction

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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 × 106) 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-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 < 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.