title: 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.affiliation: †Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, No. 27, Taiping Road, Beijing 100850, China.|∥Department of Stomatology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100071, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Shu
authors.affiliation: †Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, No. 27, Taiping Road, Beijing 100850, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Hao
authors.affiliation: §Department of Polymer Science and Key Laboratory of Systems Bioengineering of Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China.
authors.forename: Fanglian
authors.initials: F
authors.lastname: Yao
authors.affiliation: ⊥Department of Chemistry and Biochemistry, University of Texas at Austin, 2500 Speedway, Austin, Texas 78712, United States.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Qian
authors.affiliation: †Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, No. 27, Taiping Road, Beijing 100850, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: †Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, No. 27, Taiping Road, Beijing 100850, China.|§Department of Polymer Science and Key Laboratory of Systems Bioengineering of Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China.
authors.forename: Boguang
authors.initials: B
authors.lastname: Yang
authors.affiliation: †Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, No. 27, Taiping Road, Beijing 100850, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Li
authors.affiliation: †Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, No. 27, Taiping Road, Beijing 100850, China.
authors.forename: Changyong
authors.initials: C
authors.lastname: Wang
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry*; D000091342:Endoplasmic Reticulum Chaperone BiP; D006321:Heart / Q000254:growth & development / Q000503:physiopathology*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage / Q000737:chemistry*; D000860:Hypoxia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D018919:Neovascularization, Physiologic; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D023822:Tissue Engineering / Q000295:instrumentation*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D010455:Peptides; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D048271:Chitosan; D051057:Proto-Oncogene Proteins c-akt
keywords: RoY peptide; angiogenesis; cardiac tissue engineering; chitosan; hypoxia