Angiogenesis induced by growth factor-releasing microspheres can be an off-the-shelf and immediate alternative to stem cell therapy for acute myocardial infarction (AMI), independent of stem cell yield and comorbidity-induced dysfunction. Reliable and prolonged local delivery of intact proteins such as VEGF is, however, notoriously difficult. Our objective was to create a platform for local angiogenesis in human-sized hearts, using polyethylene-glycol/polybutylene-terephthalate (PEG-PBT) microsphere-based VEGF<inf>165A</inf> delivery. PEG-PBT microspheres were biocompatible, distribution was size dependent, and a regimen of 10 × 106 15-×m microspheres at 0.5 × 10<sup>6</sup>/min did not induce cardiac necrosis. Efficacy, studied in a porcine model of AMI with reperfusion rather than chronic ischemia used for most reported VEGF studies, shows that microspheres were retained for at least 35 days. Acute VEGF<inf>165A</inf> release attenuated early cytokine release upon reperfusion and produced a dose-dependent increase in microvascular density at 5 wk following AMI. However, it did not improve major variables for global cardiac function, left ventricular dimensions, infarct size, or scar composition (collagen and myocyte content). Taken together, controlled VEGF<inf>165A</inf> delivery is safe, attenuates early cytokine release, and leads to a dose-dependent increase in microvascular density in the infarct zone but does not translate into changes in global or regional cardiac function and scar composition.

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American Journal of Physiology - Heart and Circulatory Physiology
Department of Cardiology

Uitterdijk, A., Springeling, T., van Kranenburg, M., van Duin, R., Krabbendam-Peters, I., Gorsse-Bakker, C., … van Beusekom, H. (2015). VEGF165A microsphere therapy for myocardial infarction suppresses acute cytokine release and increases microvascular density but does not improve cardiac function. American Journal of Physiology - Heart and Circulatory Physiology, 309(3), H396–H406. doi:10.1152/ajpheart.00698.2014