Nanoparticles loaded with hepatic growth factor and insulin-like growth factor-1 improve left ventricular repair in a porcine model of myocardial Ischemia reperfusion injury
| Autor: | Ming Wu, Stefan Janssens, Piet Claus, E Colino, Beatriz Pelacho, S. De Buck, S Cohen, Denise Veltman, Peter Pokreisz, Patricia Holemans, Ellen Caluwé, Felipe Prosper, Hilde Gillijns |
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| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
business.industry Growth factor medicine.medical_treatment Ischemia medicine.disease Insulin-like growth factor Reperfusion therapy Internal medicine medicine Cardiology Hepatocyte growth factor Myocardial fibrosis Myocardial infarction Cardiology and Cardiovascular Medicine business Reperfusion injury medicine.drug |
| Zdroj: | European Heart Journal. 41 |
| ISSN: | 1522-9645 0195-668X |
| Popis: | Introduction Nanomedicine offers great potential for treatment of cardiovascular disease. We tested whether intramyocardial (IM) injection of pro-angiogenic hepatocyte growth factor (HGF) and anti-apoptotic, pro-myogenic insulin-like growth factor 1 (IGF-1) encapsulated in Alginate-Sulfate nanoparticles (AlgS-NP) improves left ventricular (LV) functional recovery in a porcine ischemia-reperfusion (I/R) model. Methods Myocardial infarction (MI) was induced by 75min balloon occlusion of the mid-LAD followed by reperfusion. After 1w, pigs (n=12) with marked LV dysfunction (EF Results At 1w after MI, LV ejection frqction (LVEF) was 37±5% (range 27–45%) and infarct size (IS)/LV mass 24±6% (range 19–38%). Myocardial retention of AlgS-NP was comparable between 2 groups (maximal systemic leakage after IM injection: 9% CON vs 20% GF, P=0.25). After 8 w, IS/LV mass decreased by one third in GF-treated pigs compared with 14% in CON (P=0.03, Fig. A) and was associated with a trend towards improvement in CFR (P=0.05, Fig. B). LVEF significantly increased in GF-treated pigs (6±2% vs. −1±1%, P=0.02, Fig. C), which was attributable to a greater reduction in end-systolic volume. The improvement in LVEF was also consistent with significant reduction of fibrosis (P=0.01, Fig. D) in the peri-infarct zone (PI). Conclusions Intramyocardial injection of AlgS-nanoparticle-encapsulated HGF and IGF-1 to the ischemic myocardium significantly improves LV repair, and offers the prospect of innovative treatment for patients with refractory ischemic heart disease. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): EuroNanoMed, Horizon 2020 |
| Databáze: | OpenAIRE |
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