Myocardial infarction (MI) is the principal cause of mortality and morbidity around the world, which is a sever threat to human health. Therapy for MI remains challenging. Vascular endothelial growth factor (VEGF) is one of the most important angiogenic factors, which triggers a series of events that inhibits cell apoptosis and also mediates mobilization and differentiation of cardiac progenitor cells. However, the non-targeted delivery of VEGF decreases its therapeutic efficacy due to an insufficient local concentration in the ischemic myocardium.
Researchers in Prof. DAI Jianwu’s group of the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, used a specific peptide to modify VEGF and determined that this modified VEGF (IMT-VEGF) localized to the ischemic myocardium through intravenous injection by interacting with cardiac troponin I (cTnI).
When IMT-VEGF was used to mediate cardiac repair in a rat model of ischemia-reperfusion injury, a decreased scar size, enhanced angiogenesis and improved cardiac function was observed. Moreover, an alternative treatment using the repeated administration of a low-dose IMT-VEGF also promoted angiogenesis and functional recovery.
The therapeutic effects of IMT-VEGF were further confirmed in a pig model of MI as the result of the conserved properties of its interacting protein, cTnI. Compared to intramyocardial or intracoronary delivery, the targeted delivery of IMT-VEGF via intravenous injection did not require surgical treatment and could be broadly used in VEGF-based MI therapies.
These results suggested a promising therapeutic strategy for MI based on the targeted delivery of IMT-VEGF.
This study has been published on line in the Journal of Controlled Release (DOI: 10.1016/j.jconrel.2015.06.036). This work was supported by National Natural Science Foundation of China and Strategic Priority Research Program of the Chinese Academy of Sciences.
