Angiogenic effects of sequential release of VEGF-A(165) and PDGF-BB with alginate hydrogels after myocardial infarction
2007 (English)In: Cardiovascular Research, ISSN 0008-6363, E-ISSN 1755-3245, Vol. 75, no 1, 178-185 p.Article in journal (Refereed) Published
Objective: This study investigates whether local sequential delivery of vascular endothelial growth factor-A(165) (VEGF-A(165)) followed by platelet-derived growth factor-BB (PDGF-BB) with alginate hydrogels could induce an angiogenic effect and functional improvement greater than single factors after myocardial infarction. Methods: Alginate hydrogels were prepared by combining high and low molecular weight alginate. Growth factor release rates were monitored over time in vitro with I-125-labelled VEGF-A(165) and PDGF-BB included in the gels. One week after myocardial infarction was induced in Fisher rats, gels with VEGF-A(165), PDGF-BB, or both were given intra-myocardially along the border of the myocardial infarction. Vessel density was analysed in hearts and cardiac function was determined by Tissue Doppler Echocardiography. In addition, the angiogenic effect of sequenced delivery was studied in vitro in aortic rings from C57B1/6 mice. Results: Alginate gets were capable of delivering VEGF-A(165) and PDGF-BB in a sustainable manner, and PDGF-BB was released more slowly than VEGF-A(165). Sequential growth factor administration led to a higher density of alpha-actin positive vessels than single factors, whereas no further increment was found in capillary density. Sequential protein delivery increased the systolic velocity-time integral and displayed a superior effect than single factors. In the aortic ring model, sequential delivery led to a higher angiogenic effect than single factor administration. Conclusions: The alginate hydrogel is an effective and promising injectable delivery system in a myocardial infarction model. Sequential growth factor delivery of VEGF-A(165) and PDGF-BB induces mature vessels and improves cardiac function more than each factor singly. This may indicate clinical utility.
Place, publisher, year, edition, pages
2007. Vol. 75, no 1, 178-185 p.
angiogenesis, growth factors, tissue engineering, ventricular function, infarction, endothelial growth-factor, molecular-weight distribution, blood-vessel formation, factor gene-therapy, factor delivery, vegf, degradation, arteriogenesis, ischemia, doppler
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:kth:diva-16754DOI: 10.1016/j.cardiores.2007.03.028ISI: 000247719800022OAI: oai:DiVA.org:kth-16754DiVA: diva2:334797
QC 201005252010-08-052010-08-052012-03-23Bibliographically approved