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Thymosin β4 released from functionalized self-assembling peptide activates epicardium and enhances repair of infarcted myocardium.
- Source :
-
Theranostics [Theranostics] 2021 Feb 20; Vol. 11 (9), pp. 4262-4280. Date of Electronic Publication: 2021 Feb 20 (Print Publication: 2021). - Publication Year :
- 2021
-
Abstract
- The epicardium plays an important role in cardiomyogenesis during development, while it becomes quiescent in adult heart during homeostasis. This study investigates the efficiency of thymosin β4 (Tβ4) release with RPRHQGVM conjugated to the C-terminus of RADA16-I (RADA-RPR), the functionalized self-assembling peptide (SAP), to activate the epicardium and repairing the infarcted myocardium. Methods: The functionalized SAP was constituted with self-assembling motif, Tβ4-binding site, and cell adhesive ligand. Myocardial infarction (MI) models of the transgenic mice were established by ligation of the left anterior descending coronary artery. At one week after intramyocardial injection of Tβ4-conjugated SAP, the activation of the epicardium was assessed. At four weeks after implantation, the migration and differentiation of epicardium-derived cells (EPDCs) as well as angiogenesis, lymphangiogenesis and myocardial regeneration were examined. Results: We found that the designer RADA-RPR bound Tβ4 and adhered to EPDCs and that Tβ4 released from the functionalized SAP could effectively activate the epicardium and induce EPDCs to differentiate towards cardiovascular cells as well as lymphatic endothelial cells. Moreover, SAP-released Tβ4 (SAP-Tβ4) promoted proliferation of cardiomyocytes. Furthermore, angiogenesis, lymphangiogenesis and myocardial regeneration were enhanced in the MI models at 4 weeks after delivery of SAP-Tβ4 along with attenuation of adverse myocardial remodeling and significantly improved cardiac function. Conclusions: These results demonstrate that sustained release of Tβ4 from the functionalized SAP can activate the epicardium and effectively enhance the repair of infarcted myocardium. We believe the delivery of SAP-Tβ4 may be a promising strategy for MI therapy.<br />Competing Interests: Competing Interests: The authors have declared that no competing interest exists.<br /> (© The author(s).)
- Subjects :
- Animals
Cell Differentiation drug effects
Cell Movement drug effects
Cell Proliferation drug effects
Endothelial Cells drug effects
Lymphangiogenesis drug effects
Mice
Mice, Transgenic
Myocardium metabolism
Myocytes, Cardiac drug effects
Neovascularization, Physiologic drug effects
Myocardial Infarction drug therapy
Myocardium pathology
Peptides pharmacology
Pericardium drug effects
Thymosin pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1838-7640
- Volume :
- 11
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Theranostics
- Publication Type :
- Academic Journal
- Accession number :
- 33754060
- Full Text :
- https://doi.org/10.7150/thno.52309