Peptide Nanofibers Ferry Vascular Endothelial Growth Factor for Heart Repair

Peptide Nanofibers Ferry Vascular Endothelial Growth Factor for Heart Repair

Angiogenic therapy is a promising approach for tissue repair and regeneration. However, recent clinical trials with protein delivery or gene therapy to promote angiogenesis have failed to provide therapeutic effects. A key factor for achieving effective revascularization is the durability of the microvasculature and the formation of new arterial vessels. Accordingly, we carried out experiments to test whether intramyocardial injection of self-assembling peptide nanofibers (NFs) combined with vascular endothelial growth factor (VEGF) could create an intramyocardial microenvironment with prolonged VEGF release to improve post-infarct neovascularization in rats. Our data showed that when injected with NF, VEGF delivery was sustained within the myocardium for up to 14 days, and the side effects of systemic edema and proteinuria were significantly reduced to the same level as that of control. NF/VEGF injection significantly improved angiogenesis, arteriogenesis, and cardiac performance 28 days after myocardial infarction. NF/VEGF injection not only allowed controlled local delivery but also transformed the injected site into a favorable microenvironment that recruited endogenous myofibroblasts and helped achieve effective revascularization. The engineered vascular niche further attracted a new population of cardiomyocyte-like cells to home to the injected sites, suggesting cardiomyocyte regeneration. Follow-up studies in pigs also revealed healing benefits consistent with observations in rats. In summary, this study demonstrates a new strategy for cardiovascular repair with potential for future clinical translation.

Injecting vascular endothelial growth factor (VEGF) into ailing hearts has been considered a potential way to repair necrotic tissue that forms due to heart attacks. The difficulty of actually performing this feat has been due to the fact that the blood stream quickly washes away anything that is in its way, and so keeping VEGF close to the myocardium requires more complicated methods.

Now a team of researchers from Taiwan has identified a way to essentially stick VEGF to the heart so that it’s not immediately taken away with the blood. They used self-assembling peptide nanofibers to create sticky latices that can hold onto VEGF and slowly release it into the heart. The team showed that in animal trials, the growth factor was being delivered to the heart up to two weeks post injection and that it led to “significantly improved angiogenesis, arteriogenesis, and cardiac performance 28 days after myocardial infarction.”

From the study abstract:

NF[peptide nanofibers]/VEGF injection not only allowed controlled local delivery but also transformed the injected site into a favorable microenvironment that recruited endogenous myofibroblasts and helped achieve effective revascularization. The engineered vascular niche further attracted a new population of cardiomyocyte-like cells to home to the injected sites, suggesting cardiomyocyte regeneration. Follow-up studies in pigs also revealed healing benefits consistent with observations in rats. In summary, this study demonstrates a new strategy for cardiovascular repair with potential for future clinical translation.

Source : http://stm.sciencemag.org/content/4/146/146ra109.abstract?sid=d764b58c-cd95-4f43-a652-e024df222b52

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