Tissue Eng Regen Med.  2018 Aug;15(4):493-502. 10.1007/s13770-018-0134-x.

Comparison of Angiogenic Activities of Three Neuropeptides, Substance P, Secretoneurin, and Neuropeptide Y Using Myocardial Infarction

• Lee J
• Song M
• Kim J
• Park Y

• KMID: 2418105
• DOI: http://doi.org/10.1007/s13770-018-0134-x

Abstract

BACKGROUND
The interplay between neurogenesis and angiogenesis is crucial during the development mediated by neuro-angiogenic morphogens. In particular, the angiogenic activity of neuropeptides and their role in tissue regeneration have long been investigated for better understanding of their biological mechanisms and further applications. However, there have been few studies for direct comparison of angiogenic activities of neuropeptides for in vitro and in vivo models. In this study, we report that direct comparison of the angiogenic activities of neuropeptide Y, secretoneurin, and substance P (SP) immobilized on hydrogels in in vitro and in vivo experiments.
METHODS
A hyaluronic acid-based hydrogel is prepared by utilizing acrylated hyaluronic acid and thiolated peptides as a crosslinker and angiogenic factors, respectively. Angiogenic activities of three neuropeptides are evaluated not only by in vitro angiogenic and gene expression assays, but also by an in vivo chronic myocardial infarction model.
RESULTS
The comparison of in vitro angiogenic activities of three peptides demonstrates that the SP-immobilized hydrogel shows a higher degree of cell network formation and angiogenic-specific genes than those of the other peptides and the control case. In addition, a three-dimensional angiogenic assay illustrates that more sprouting is observable in the SP group. Evaluation of regenerative activity in the chronic myocardial infarction model reveals that all three peptideimmobilized hydrogels induce increased cardiac function as well as structural regeneration. Among all the cases, the SP group provided the highest regenerative activity both in vitro and in vivo.
CONCLUSION
In our comparison study, the SP-immobilized hydrogel shows the highest angiogenic activity and tissue regeneration among the test groups. This result suggests that nerve regeneration factors help angiogenesis in damaged tissues, which also highlights the importance of the neuro-angiogenic peptides as an element of tissue regeneration.

Keyword

Neuro-angiogenic peptide; Hyaluronic acid-based hydrogel; Angiogenesis; Chronic heart failure

MeSH Terms

Angiogenesis Inducing Agents
Gene Expression
Hyaluronic Acid
Hydrogel
Hydrogels
In Vitro Techniques
Myocardial Infarction*
Nerve Regeneration
Neurogenesis
Neuropeptide Y*
Neuropeptides*
Peptides
Regeneration
Substance P*
Angiogenesis Inducing Agents
Hyaluronic Acid
Hydrogel
Hydrogels
Neuropeptide Y
Neuropeptides
Peptides
Substance P