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Intramyocardial delivery of VEGF165 via a novel biodegradable hydrogel induces angiogenesis and improves cardiac function after rat myocardial infarction

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Abstract

Vascular endothelial growth factor (VEGF), an independent mitogen, has been reported to induce angiogenesis and thus attenuates the damage induced by myocardial infarction (MI). VEGF165 is the most abundant and predominant isoform of VEGF. This study investigates whether this effect could be strengthened by local intramyocardial injection of VEGF165 along with a novel biodegradable Dex-PCL-HEMA/PNIPAAm hydrogel and ascertains its possible mechanism of action. Rat models of myocardial infarction were induced by coronary artery ligation. Phosphate-buffered saline (PBS group), Dex-PCL-HEMA/PNIPAAm hydrogel (Gel group), phosphate-buffered saline containing VEGF165 (VP group), and hydrogel containing VEGF165 (VPG group) were injected into a peri-infarcted area of cardiac tissue immediately after myocardial infarction, respectively. The sham group was thoracic but without myocardial infarction. The injection of VEGF165 along with a hydrogel induced angiogenesis, reduced collagen content and MI area, inhibited cell apoptosis, increased the level of VEGF165 protein and the expression of flk-1 and flt-1, and improved cardiac function compared with the injection of either alone after MI in rats. The results suggest that injection of VEGF165 along with a hydrogel acquires more cardioprotective effects than either alone in rat with MI by sustained release of VEGF165, then may enhance the feedback between VEGF and its receptors flk-1 and flt-1.

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Acknowledgement

The authors thank the contract grant sponsors National Nature Science Foundation of China (contract grant number: 81170307), National Key Basic Research Program of China (contract grant number: 2005CB623903) and The Fundamental Research Funds for the Central Universities;contract grant number: 2042014kf0130.

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Correspondence to Xuejun Jiang.

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Zhu, H., Jiang, X., Li, X. et al. Intramyocardial delivery of VEGF165 via a novel biodegradable hydrogel induces angiogenesis and improves cardiac function after rat myocardial infarction. Heart Vessels 31, 963–975 (2016). https://doi.org/10.1007/s00380-015-0710-0

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