RoY peptide-modified chitosan-based hydrogel to improve angiogenesis and cardiac repair under hypoxia.

Abstract

Myocardial infarction (MI) still represents the "Number One Killer" in the world. The lack of functional vasculature of the infracted myocardium under hypoxia is one of the main problems for cardiac repair. In this study, a thermosensitive chitosan chloride-RoY (CSCl-RoY) hydrogel was developed to improve angiogenesis under hypoxia after MI. First, RoY peptides were conjugated onto the CSCl chain via amide linkages, and our data show that the conjugation of RoY peptide to CSCl does not interfere with the temperature sensitivity. Then, the effect of CSCl-RoY hydrogels on vascularization in vitro under hypoxia was investigated using human umbilical vein endothelial cells (HUVECs). Results show that CSCl-RoY hydrogels can promote the survival, proliferation, migration and tube formation of HUVECs under hypoxia compared with CSCl hydrogel. Further investigations suggest that CSCl-RoY hydrogels can modulate the expression of membrane surface GRP78 receptor of HUVECs under hypoxia and then activate Akt and ERK1/2 signaling pathways related to cell survival/proliferation, thereby enhancing angiogenic activity of HUVECs under hypoxia. To assess its therapeutic properties in vivo, a MI model was induced in rats by the left anterior descending artery ligation. CSCl or CSCl-RoY hydrogels were injected into the border of infracted hearts. The results demonstrate that the introduction of RoY peptide can not only improve angiogenesis at MI region but also improve the cardiac functions. Overall, we conclude that the CSCl-RoY may represent an ideal scaffold material for injectable cardiac tissue engineering.

• Authors: Yao Shu, Tong Hao, Fanglian Yao, Yufeng Qian, Yan Wang, Boguang Yang, Junjie Li, Changyong Wang
• Journal: ACS applied materials & interfaces (ACS Appl Mater Interfaces) Vol. 7 Issue 12 Pg. 6505-17 (Apr 01 2015) ISSN: 1944-8252 [Electronic] United States
• PMID: 25756853 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Endoplasmic Reticulum Chaperone BiP
• HSPA5 protein, human
• Heat-Shock Proteins
• Peptides
• Hydrogel, Polyethylene Glycol Dimethacrylate
• Chitosan
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Cell Proliferation
• Cell Survival
• Chitosan (administration & dosage, chemistry)
• Endoplasmic Reticulum Chaperone BiP
• Heart (growth & development, physiopathology)
• Heat-Shock Proteins (genetics, metabolism)
• Human Umbilical Vein Endothelial Cells (cytology, metabolism)
• Humans
• Hydrogel, Polyethylene Glycol Dimethacrylate (administration & dosage, chemistry)
• Hypoxia (drug therapy, genetics, metabolism, physiopathology)
• Male
• Myocardial Infarction (drug therapy, genetics, metabolism, physiopathology)
• Neovascularization, Physiologic
• Peptides (administration & dosage, chemistry)
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction
• Tissue Engineering (instrumentation)
• Tissue Scaffolds (chemistry)