title: Intramyocardial Delivery of Notch Ligand-Containing Hydrogels Improves Cardiac Function and Angiogenesis Following Infarction.
abstract: Myocardial infarction (MI) is the leading cause of death worldwide. Notch1 signaling plays a critical role in cardiac development, in survival, cardiogenic lineage commitment, differentiation of cardiac stem/progenitor cells, and in regenerative responses following myocardial injury. The objective of this study was the evaluation of the therapeutic effect of delivering the Notch ligand-containing hydrogels in a rat model of MI. Self-assembling peptide (SAP) hydrogels were functionalized with a peptide mimic of the Notch1 ligand Jagged1 (RJ). In rats subjected to experimental MI, delivery of RJ-containing hydrogel to the infarcted heart resulted in improvement in cardiac function back to sham-operated levels. A significant decrease in fibrosis and an increase in the endothelial vessel area and Ki67 expression were also observed in rats treated with the RJ hydrogels compared to untreated rats or rats treated with unmodified or scrambled peptide hydrogels. This study demonstrates the functional benefit of Notch1-activating peptide delivered in SAP hydrogels for cardiac repair.
authors.affiliation: 1 Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology , Atlanta, Georgia .|2 Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology , Atlanta, Georgia .|3 Children's Heart Research and Outcomes Center, Children's Healthcare of Atlanta and Emory University , Atlanta, Georgia .
authors.forename: Archana V
authors.initials: AV
authors.lastname: Boopathy
authors.affiliation: 1 Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology , Atlanta, Georgia .|3 Children's Heart Research and Outcomes Center, Children's Healthcare of Atlanta and Emory University , Atlanta, Georgia .|4 Division of Cardiology, Emory University School of Medicine , Atlanta, Georgia .
authors.forename: Mario D
authors.initials: MD
authors.lastname: Martinez
authors.affiliation: 1 Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology , Atlanta, Georgia .|3 Children's Heart Research and Outcomes Center, Children's Healthcare of Atlanta and Emory University , Atlanta, Georgia .
authors.forename: Amanda Walker
authors.initials: AW
authors.lastname: Smith
authors.affiliation: 1 Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology , Atlanta, Georgia .|3 Children's Heart Research and Outcomes Center, Children's Healthcare of Atlanta and Emory University , Atlanta, Georgia .|4 Division of Cardiology, Emory University School of Medicine , Atlanta, Georgia .
authors.forename: Milton E
authors.initials: ME
authors.lastname: Brown
authors.affiliation: 1 Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology , Atlanta, Georgia .|2 Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology , Atlanta, Georgia .|5 George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology , Atlanta, Georgia .
authors.forename: Andrés J
authors.initials: AJ
authors.lastname: García
authors.affiliation: 1 Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology , Atlanta, Georgia .|2 Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology , Atlanta, Georgia .|3 Children's Heart Research and Outcomes Center, Children's Healthcare of Atlanta and Emory University , Atlanta, Georgia .|4 Division of Cardiology, Emory University School of Medicine , Atlanta, Georgia .
authors.forename: Michael E
authors.initials: ME
authors.lastname: Davis
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005355:Fibrosis; D006334:Heart Function Tests / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D020100:Hydrogels / Q000494:pharmacology*; D019394:Ki-67 Antigen / Q000378:metabolism; D008024:Ligands; D009203:Myocardial Infarction / Q000150:complications / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D051880:Receptors, Notch / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects
chemical_list: D020100:Hydrogels; D019394:Ki-67 Antigen; D008024:Ligands; D051880:Receptors, Notch